Anticancer gene - Knowledge

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genetic material in the cell can be repaired, or if the cell should be destroyed through apoptosis. The individual topologically associating domains (TADs) target different genes and unique effector pathways. It has been observed that inactivating both of the TADs detrimentally affects the ability of p53 to suppress tumor growth and interact with target genes. When only one TAD is inactivated, p53 can still suppress specific tumors; however, it can no longer successfully engage in transactivation. The C-terminal domain (CTD) is an intrinsically disordered domain (IDD), which can take on different conformations depending on what it is binding with and is a location of many

710:) was used to isolate the unique non-hemolytic defensin known as brevinin-2R. Malignant cells such as T-cell leukemia Jurkat, B-cell lymphoma BJAB, colon cancers HT29/219, SW742, fibrosarcoma L929, breast cancer MCF-7, and A549 (lung carcinoma) exhibit preferential cytotoxicity towards it in comparison to primary cells such T cells, human lung fibroblasts, and peripheral blood mononuclear cells (PBMC). Jurkat, MCF-7, and L929 overexpressing cells as well as MCF-7 cells overexpressing a dominant-negative mutant of a pro-apoptotic BNIP3 (TM-BNIP3) were largely resistant to Brevinin-2R treatment. 1546:, resulting in its ability to regulate p53 function depending on what it is bound to and what modifications are linked with the CTD. This domain also aids in the binding of the central DNA-binding domain (DBD) to specific DNA sequences; the CTD is a positive regulator of DNA binding and stabilizes the interaction of the DNA with the DBD. p53 is unique as a transcription factor in that it can recognize and bind response elements (RE) in many different environments and doesn't need other transcription factors to cooperatively bind with it like many other TFs. 780:-independent manner; however, there is still communication between this pathway and the caspase-dependent apoptosis pathway. In the context of cancer, E4orf4 is even more efficient at inducing cell death than in healthy cells, which could be an important finding for potential cancer therapies. It has been discovered that the mechanisms behind the function of E4orf4 are closely associated with several other proteins including the B55 subunit of PP2A. E4orf4 binds to PP2A to reduce the phosphorylation of the 727:

ATP levels while simultaneously increasing the concentration of reactive oxygen species. Currently and somewhat unrelated, Brevinin-2R is being considered for diabetic treatments. In treating type II diabetes, or diabetes mellitus, Brevinins have been shown to promote insulin release. Finally, these peptides even have the capability to increase the rate of tissue regeneration, as seen with the frog in which Brevinin-2R was isolated from.

1585:. Specifically, this impacts children and young adults. A majority of these mutations in the TP-53 gene are single amino acid changes, but other mutations cause a small portion of the DNA to be absent. This leads to a faulty p53 protein that fails to recognize DNA damage in cells, control cell growth, and initiate apoptosis in cells with damaged DNA. Consequently, cells containing erroneous DNA can uncontrollably divide. 1488: 820: 36: 1342:) is a tumor suppressor protein with a pro-apoptotic function. Par-4 was first discovered in rat prostate cancer cells as part of an effort determined in discovering genes that were induced in response to increased Ca in cells, although it is now known to be ubiquitously expressed in a wide variety of tissues across many different species. The Par-4 gene is located on the minus strand of 686: 1141:, and several other organs, it initiates apoptosis through Bax-mediated mitochondrial-dysfunction through the inhibition of the Bcl2 family's antiapoptotic members. Through gene knockout studies, it was shown that double deficient Noxa there was no spontaneous tumor development as commonly observed with knockout of p53. Noxa has been shown to be involved in the maintenance of memory 1423: 631: 1626: 1594:

gene alterations. The likelihood that a woman may develop ovarian and breast cancer is increased by certain gene abnormalities. Male breast cancer and prostate cancer risk are both increased by BRCA2 gene mutations Men and women with BRCA2 gene mutations have a marginally increased chance of acquiring pancreatic cancer. (53)

1250:. The ORCTL3 gene spans around 12 kb of genomic DNA and consists of ten exons. It was shown that the 2.4 kb transcript of this gene is universally expressed in all human tissues. Additionally, ORCTL3 transfection into numerous tumorigenic cells induced apoptosis, while normal and primary cells remained healthy. 1373:

is a 38 kDa multi-domain protein composed of about 340 amino acids. Conserved domains among human, mouse, and rat homologs include the leucine zipper (LZ) domain at the C-terminal region, two nuclear localization sequences, NLS1 and NLS2, in the N-terminal region, and a nuclear export sequence within

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state causes dormant apoptotic signals to be initiated and cause cell death to be more easily achieved by different signals. 2) There has been some indication that cancer cells become addicted to oncogenic pathways. E4orf4 may inhibit these pathways, causing cell death in cancer cells, but not normal

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to induce cell death. Modeling of this protein reveals that it is likely made up of 3 α-helices with N- and C-terminal loops. It has a small stretch of amino acids in positions 66–75, which are highly basic, and likely are a place of nuclear and nucleolar targeting, as well as a place for Src kinases

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This defensin traditionally works as a part of the innate immune system, working as an antimicrobial defense. However, this peptide is currently being studied as an anticancer peptide. Brevinin-2R works to trigger cell death by reducing the mitochondrial membrane potential resulting in lower cellular

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can detect early changes that lead to cancer and can convert survival signals in cancer cells into signals for cell death. It interacts with various proteins, such as DEDAF, Nur77, Nmi, Hippi, and APC1. Studies using animal models and genetically modified mice have demonstrated that apoptin is a safe

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NS1 is considered a regulatory protein due to its activity in transcription, translation, and protein-protein interactions, which allows the parvovirus to replicate unhindered. However, scientists are primarily interested in utilizing its cytolytic activity since this has been proven to be active in

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Upon receiving intrinsic death signals, the gene NOXA encodes for the protein Noxa through a three-exon transcript. This protein binds to anti-apoptotic proteins resulting in these proteins' inhibition. As a p53 inducible gene, NOXA is transcribed and translated to Noxa in response to DNA damage and

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The intrigue surrounding TRAIL is all due to this protein's ability both in vivo and in vitro to specifically target tumor cells for apoptosis while leaving healthy cells intact. This activity proceeds by both the intrinsic and extrinsic pathway. First, the homotrimer of TRAIL binds three molecules

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These 25 amino acid peptides, in contrast to the majority of peptides within the Brevinine family, have low hemolytic action. Not only does the peptide have a reduced hemolytic action, it also is semi-selective towards cancer cells and leaves non-cancerous cells largely unharmed. This peptide works

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The p53 protein is a tumor-suppressing transcription factor (TF), which can recognize when there is an alteration in a cell's DNA caused by factors including chemical toxins, radiation, ultraviolet (UV) rays, and other damaging agents. Crucially, p53 plays a role in determining whether the damaged

1451:. It was discovered in 1995 by Wiley et al. and then further characterized in 1996 by Pitti et al. The former study discovered that TRAIL is localized to surfaces of cells in most human tissues, excluding the brain, liver, and testes, while the latter study was able to elicit that the protein is a 1164:

was discovered by Dr. Helene Toolan to have an oncosuppressive activity. However, the specific gene found in the parvovirus genome, which is called NS1, that causes the oncosuppressive activity was not characterized until later. NS1 is a small protein (only 672 amino acids) with 5 distinct domains

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is a group of diseases where cells multiply uncontrollably. Normally, cells have a built-in process called apoptosis that triggers cell death to prevent excessive growth. However, when these processes are disrupted, cancer can develop. Studies show that cancer is one of the leading causes of death

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The tumor suppressing BRCA genes frequently help in cancer prevention. They control how cells divide and develop and help repair DNA damage BRCA gene abnormalities, however, can the likelihood of having specific cancers is raised. Cancers BRCA1 and BRCA2 are the two BRCA recognized cancer-causing

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The anticancer function of Par-4 is achieved by two distinct means: activating the molecular components of the cell-death machinery and inhibiting pro-survival factors. One essential apoptotic function of Par-4 is inhibiting the NF-κB pathway, which is a key contributing factor in many tumors and

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is unique in its ability to attack cancerous cells while sparing normal ones. It induces apoptosis through a pathway that involves mitochondria but does not rely on the p53 protein or death receptors typically involved in cell death. In healthy cells, apoptin stays in the cytoplasm, but in cancer

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out of Princeton University. Further papers came out around the same time all mentioning the discovery of a tumor-suppressing protein. While p53 was first officially identified in 1979, many labs in previous years had come across the same protein, without knowing what it was. In the mid-1970s, a

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E4orf4 is an important regulator of adenoviruses. Additionally, outside of the context of the virus, it causes programmed cell death both in the context of a healthy cellular environment, and cancer. E4orf4 is a key regulator of Ad by down-regulating both viral and cellular genes, which plays an

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pathway in a similar fashion as HAMLET that results in the release of cytochrome c from the mitochondria, which then causes the activation of effector caspase. The latter mechanism is the focus of many oncogenic therapies because p53, the tumor suppressor gene, activates the same pathway. Since

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ORCTL3 is a 90 kDa protein composed of 351 amino acids. It is suggested that the protein spans the cell membrane several times, based on computational methods. Overexpressed ORCTL3 is localized to the endoplasmic reticulum (ER), Golgi and the plasma membrane but not to mitochondria. ORCTL3 was

1581:, and other cancers often due to a single point mutation in p53. Li-Fraumeni Syndrome is a condition linked to inherited mutations, at least 140 mutations, in the TP-53 gene. This condition largely increases the risk of developing cancers like breast cancer, bone cancer, and 832:

HAMLET is known as an anticancer protein complex found in breast milk. One of the two molecules of this complex is multimeric alpha lactalbumin (MAL), which was first discovered during a study in 1995 that investigated how breast milk affects bacteria transformed with

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junction, causing a stress response in the cell. Specifically, NS1 interacts with many molecules and compounds important in the transition and inhibits their activity. When NS1 expression reaches a certain threshold, the triggered stress response finally causes

1504:; this protein is a tumor suppressor. p53 was discovered in 1979 stemming from a study involving cancer immunology and the role of viruses in some cancers. The protein was so named because it was measured to have a weight of 53 kDa. This study was conducted by 784:(DDR) proteins. Consequently, this reduces the function of DDR and limits DNA repair. Many cancer cells have defects in the DDR pathways and targeting these cells with E4orf4 can potentially destroy the remaining DDR pathways, resulting in cancer cell death. 802:

model demonstrated that E4orf4 can inhibit classical apoptosis in healthy tissues. It has been considered that this function of E4orf4 is lost in cancer cells causing a more effective killing of cells. 6) E4orf4 has been shown to cause structural changes in

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is a common treatment that uses drugs to kill cancer cells. It works by damaging the DNA of cancer cells or stopping them from dividing. This process can also impact genes that control cell growth, affecting both cancer-causing and anticancer genes.

1036:; it has been seen that following this, apoptosis is induced only in the tumor cells and results in no toxicity in the healthy cells. Its function as a tumor suppressor is not fully understood, but it has been observed that in the context of 3340:

Moreno-Bueno, Gema; Fernandez-Marcos, Pablo J.; Collado, Manuel; Tendero, Mercedes J.; Rodriguez-Pinilla, Socorro M.; Garcia-Cao, Isabel; Hardisson, David; Diaz-Meco, Maria T.; Moscat, Jorge; Serrano, Manuel; Palacios, Jose (2007-03-01).

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are targeted by HAMLET through a mechanism that is less understood. Research does suggest that HAMLET directly binds to the proteasome leading to its inhibition. Third, HAMLET has been found to target the nucleus, specifically

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Christensen J, Cotmore SF, Tattersall P (1995) Minute virus of mice transcriptional activator protein NS1 binds directly to the transactivation region of the viral P38 promoter in a strictly ATP-dependent manner. J Virol

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and is able to regulate cell death through a variety of intracellular stress signals. Having been discovered nearly three decades ago in 1990 by Hijikata et al., this gene product was isolated this protein from an

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Hristov G, Kramer M, Li J, El-Andaloussi N, Mora R, Daeffler L et al (2010) Through its nonstructural protein NS1, parvovirus H-1 induces apoptosis via accumulation of reactive oxygen species. J Virol 84:5909–5922

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the LZ domain. Although Par-4 mutations are rare, it was identified that an A to T point mutation affecting residue 189 localized in exon 3 causes premature termination of Par-4 in human endometrial carcinoma.

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or larger rearrangements that affect the gene's function. When these anticancer genes are lost or altered, it can disrupt their ability to control cell growth, potentially leading to the development of cancer.

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Murata, Yasushi; Tamari, Mayuml; Takahashl, Takashi; Horio, Yoshltsugu; Hlbi, Kenji; Yokoyama, Shiro; Inazawa, Johjl; Yamakawa, Kazuhiro; Ogawa, Akimi; Takahashi, Toshitada; Nakamura, Yusuke (1994-08-01).

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Cook, Jason; Krishnan, Sumathi; Ananth, Subbian; Sells, Stephen F.; Shi, Yang; Walther, McClellan M.; Linehan, W. Marston; Sukhatme, Vikas P.; Weinstein, Michael H.; Rangnekar, Vivek M. (February 1999).

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Olugbami, Jeremiah. "A comparative assessment of antiproliferative properties of resveratrol and ethanol leaf extract of Anogeissus leiocarpus (DC) Guill and Perr against HepG2 hepatocarcinoma cells".

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of either TRAIL-receptor 1 or 2, which are transmembrane proteins that contain a cytoplasmic death domain. Once TRAIL is bound, Fas, caspase-8, and caspase-10 associate with the death domain forming

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Toolan, H.W., Rhode, S.L. and Gierthy, J.F. (1982) Inhibition of 7, 12-dimethylbenz(a)anthracene-induced tumors in Syrian hamsters by prior infection with H-l parvovirus. Cancer Res. 42,2552- 25.55.

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thus activating the extrinsic death pathway. Overexpression of Par-4 selectively induces apoptosis in cancer cells, attributed to the selective activation via phosphorylation of the T155 residue by

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that exert different functions that inevitably lead to apoptosis and cell death. NS1 activates cell death through two different pathways, apoptosis/lysosomal-like programmed cell death and necrosis/

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Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 1996;271:12687–90.

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and effective anticancer agent, capable of significantly reducing tumor size. It holds promise for future cancer therapies as a treatment target and an early indicator of tumor-specific processes.

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Dent, Paul; Yacoub, Adly; Hamed, Hossein A.; Park, Margaret A.; Dash, Rupesh; Bhutia, Sujit K.; Sarkar, Devanand; Gupta, Pankaj; Emdad, Luni; Lebedeva, Irina V.; Sauane, Moira (September 2010).

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activity. Par-4 overexpression is sufficient to induce apoptosis in most cancer cells in the absence of a second apoptotic signal, but does not induce apoptosis in normal or immortalized cells.

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prevents cell death by activating the expression of pro-survival genes. Par-4 also assists in PCD by enabling the trafficking of specific ligands such and cell surface death receptors, such as

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Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995;3:673–82

861:, a subsection of the TNF pathway, through targeting many different cell components. First, after uptake by the cell, HAMLET proceeds to the mitochondria and depolarize the membranes at 3390:

García-Cao, Isabel; Duran, Angeles; Collado, Manuel; Carrascosa, Maria J; Martín-Caballero, Juan; Flores, Juana M; Diaz-Meco, Maria T; Moscat, Jorge; Serrano, Manuel (2005-06-01).

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The main mechanism behind the specificity of cancer cell targeting by E4orf4 is unknown but there are multiple hypotheses that scientists are considering: 1) The activation of the

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AbuAli, G.; Chaisaklert, W.; Stelloo, E.; Pazarentzos, E.; Hwang, M.-S.; Qize, D.; Harding, S. V.; Al-Rubaish, A.; Alzahrani, A. J.; Al-Ali, A.; Sanders, T. a. B. (March 2015).

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project in search of genes with a tumor-specific apoptosis activity. The name ORCTL3 was decided upon because of its structural homology to proteins belonging to the family of

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transformed cells might explain the tumor-specificity of ORCTL3 to some extent, however, the existence of other additional targets of ORCTL3 cannot formally be ruled out.

837:. This study found that transformed cells were selected for apoptosis at a much higher rate than the untransformed, healthy cells. A later study in 2000, ascertained that 2957:

Bahn, Andrew; Hagos, Yohannes; Reuter, Stefan; Balen, Daniela; Brzica, Hrvoje; Krick, Wolfgang; Burckhardt, Birgitta C.; Sabolić, Ivan; Burckhardt, Gerhard (2008-06-13).

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Nuesch JP, Lachmann S, Rommelaere J (2005) Selective alterations of the host cell archi- tecture upon infection with parvovirus minute virus of mice. Virology 331:159–174

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Jamadi, Robab (2020). "Anticancer Activity of Brevinin-2R Peptide and its Two Analogues Against Myelogenous Leukemia Cell Line as Natural Treatments: An In Vitro Study".

649: 841:, a C18:1 fatty acid, is a cofactor that binds to MAL forming HAMLET. This complex, in a partially unfolded state, then displays apoptotic activity in cancer cells. 1215:

through an unknown mechanism. The last NS1-mediated mechanism of cytolysis involves the depolarization of the mitochondria. This results in the release of many

1346:, spanning 99.06 kb of DNA and containing seven exons and six introns. Par-4 is known to be downregulated in certain terminally differentiated cells such as 2252:

Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina (2008), Bösze, Zsuzsanna (ed.),

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The American Society for Clinical Oncology. Cancer Genetics in 2015: http://www.cancer.net/navigating-cancer-care/cancer-basics/genetics/cancer-genetics.

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Toolan, H.W., Saunders, E.L., Southam, C.M., Moore, A.E. and Levin, A.G. (1965) H-l virus viremia in the human. Proc. Sot. Exp. Biol. Med. 119, 711-715.

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scientist by the name of Peter Tegtmeyer happened upon a protein with an approximate size of 50 kDa. However, because he was focusing his studies on

1516:. This information was corroborated during the same year when a separate study found that p53 had immunoreactivity with serum from tumors containing 2628:

Toolan, H.W. and Ledinko, N. (1968) Inhibition by H-l virus of the incidence of tumors produced by adenovirus 12 in hamsters. Virology 35, 475478.

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cells. 3) E4orf4 may use oncogenes that have been activated in cancer cells, including Src, to cause cell death. 4) Cancer cells have disrupted

2787:"Molecular cloning, mapping, and characterization of two novel human genes, ORCTL3 and ORCTL4, bearing homology to organic-cation transporters" 2709:

Nuesch JP, Bar S, Rommelaere J (2008) Viral proteins killing tumor cells: new weapons in the fight against cancer. Cancer Biol Ther 7:1374–1376

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of Par-4 in mice leads to the development of spontaneous tumors in various tissues revealed by increased proliferative response of peripheral

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Toolan, H.W. and Ledinko, N. (1965) Growth and cytopathogenicity of H-viruses in human and simian cell cultures. Nature 208, 8 12-8 13.

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Nüesch, Jürg P. F.; Rommelaere, Jean (2014). "Tumor Suppressing Properties of Rodent Parvovirus NS1 Proteins and Their Derivatives".

949:. It has been found that its expression is either not present or present at very low levels in tumor cells, including advanced stage 1268: 667: 119: 3223:

Kögel, D.; Reimertz, C.; Mech, P.; Poppe, M.; Frühwald, M. C.; Engemann, H.; Scheidtmann, K. H.; Prehn, J. H. M. (December 2001).

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cancer is commonly caused by the inactivation of p53, TRAIL could mediate this effect by still activating the apoptotic pathway.

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Carlo-Stella, Carmelo; Lavazza, Cristiana; Locatelli, Alberta; Viganò, Lucia; Gianni, Alessandro M.; Gianni, Luca (2007-04-15).

1246:. However, the name is a misnomer as after examining the properties of ORCTL3, it was revealed that ORCTL3 is a transporter for 886:

condensation, which inevitably causes apoptosis. Lastly, studies show that cells treated by HAMLET exhibit behaviors common to

2534:"A review of the role of Puma, Noxa, and Bim in the tumorigenesis therapy and drug resistance of chronic lymphocytic leukemia" 100: 1097: 57: 1468:

that proceeds through two different mechanisms depending on the cell type. In one cell type, DISC can directly activate the

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Mechanisms of apoptosis induced by a protein complex isolated from human milk : With focus on the role of mitochondria

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family because of similar structure and amino acid sequence to other interleukins in that class, the chromosomal location (

865:. Consequently, mitochondria-dependent apoptosis factors are released as well as the caspase cascade is activated. Second, 2408:

GUPTA, P; SU, Z; LEBEDEVA, I; SARKAR, D; SAUANE, M; EMDAD, L; BACHELOR, M; GRANT, S; CURIEL, D; DENT, P (September 2006).

1618:. The genes serve as codes and blueprints to create either proteins of interest, or various non-coding ribonucleic acids ( 1044:

expression is drastically decreased. While there are no official studies published backing this claim, it is thought that

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worldwide. Despite this, recent advancements in treatment have significantly increased survival rates for many patients.

1101: 3449:"Par-4 Drives Trafficking and Activation of Fas and FasL to Induce Prostate Cancer Cell Apoptosis and Tumor Regression" 79: 1410:(PKA). It has been shown that two events are required for Par-4 activation: nuclear entry and phosphorylation by PKA. 993:, cause immune-regulation, and increase radiation lethality. It was seen in one Phase I clinical trial that injecting 3225:"Dlk/ZIP kinase-induced apoptosis in human medulloblastoma cells: requirement of the mitochondrial apoptosis pathway" 1904:"Biological Properties, Current Applications and Potential Therapeutic Applications of Brevinin Peptide Superfamily" 1178:

cancerous cells. The first way NS1 propagates cell death through cytolysis is by interrupting the cell cycle at the

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protein of 14kDa which regulates growth in all stages of the adenovirus (Ad) infection. E4orf4 partners mainly with

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or changes in these genes can occur, which might lead to cancer. These changes can include small alterations in the

1473: 1017: 3879: 1304: 1100:(ATL) library This gene, and its protein in which it encodes for, has been studied as a potential therapeutic in 603: 592: 86: 1836:"Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems" 1362:. Par-4 has also been shown to be generally higher in dying cells, consistent with its pro-apoptotic functions. 1834:

Malla, Waseem Akram; Arora, Richa; Khan, Raja Ishaq Nabi; Mahajan, Sonalika; Tiwari, Ashok Kumar (2020-06-25).

1452: 1387: 958: 811: 3285:"Identification of a Unique Core Domain of Par-4 Sufficient for Selective Apoptosis Induction in Cancer Cells" 2048:

Brestovitsky, Anna; Nebenzahl-Sharon, Keren; Kechker, Peter; Sharf, Rakefet; Kleinberger, Tamar (2016-02-11).

3861:. Cancer Research UK; 2014: http://www.cancerresearchuk.org/about-cancer/what-is-cancer/genes-dna-and-cancer. 3793:

Li, Lijuan; Wu, Jian; Sima, Xiutian; Bai, Peng; Deng, Wei; Deng, Xueke; Zhang, Lin; Gao, Linbo (2013-03-17).

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Nalca, Aysegul; Qiu, Shirley Guofang; El-Guendy, Nadia; Krishnan, Sumathi; Rangnekar, Vivek M. (1999-10-15).

2740:"Characterization of an 800 kb region at 3p22-p21.3 that was homozygously deleted in a lung cancer cell line" 3283:

El-Guendy, Nadia; Zhao, Yanming; Gurumurthy, Sushma; Burikhanov, Ravshan; Rangnekar, Vivek M. (2003-08-15).

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to present tumor antigens, resulting in an immune response against tumors. It has also been discovered that

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important role in regulating the proliferation of the virus. In turn, the down-regulation also impacts the

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protein, also known as viral protein 3 (VP3), was first isolated from chickens and has been found to cause

2260:, Advances in Experimental Medicine and Biology, vol. 606, New York, NY: Springer, pp. 217–240, 1642: 2346:

Düringer, Caroline; Hamiche, Ali; Gustafsson, Lotta; Kimura, Hiroshi; Svanborg, Catharina (2003-10-24).

982: 854: 793: 747: 546: 156: 2254:"Apoptosis and Tumor Cell Death in Response to HAMLET (Human α-Lactalbumin Made Lethal to Tumor Cells)" 3447:

Chakraborty, Mala; Qiu, Shirley Guofang; Vasudevan, Krishna Murthi; Rangnekar, Vivek M. (2001-10-01).

3119: 2195: 2128: 1685: 1582: 1533:, a tumor-causing virus affecting monkeys and humans, he did not pay much attention to this protein. 1283: 965:

expression in tumor cells results in growth arrest and cell death in many different cell lines. When

765: 611: 610:. Current therapeutic agents using apoptin have shown effectiveness in treating types of cancer like 532: 2050:"The Adenovirus E4orf4 Protein Provides a Novel Mechanism for Inhibition of the DNA Damage Response" 3543:

Gurumurthy, Sushma; Goswami, Anindya; Vasudevan, Krishna Murthi; Rangnekar, Vivek M. (2005-02-01).

2663:. Advances in Experimental Medicine and Biology. Vol. 818. London: Springer. pp. 99–124. 1276: 1272: 1208: 1049: 989:

has been used in several clinical trials because of its ability to induce apoptosis, prevent tumor

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is mostly found in the nucleus and is activated, while in normal cells, it remains inactive in the

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Sullivan, Kelly D.; Galbraith, Matthew D.; Andrysik, Zdenek; Espinosa, Joaquin M. (January 2018).

807:, which could impact metabolic reprogramming and may affect cancer and healthy cells differently. 555:

works by causing apoptosis, or cell death, specifically in tumor cells that lack a protein called

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without harming healthy ones. They do this through processes like programmed cell death, known as

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transcription factors. However, the STAT pathway is not always activated and is not required for

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via an adenovirus directly into a tumor resulted in safe tumor regulation and immune activation.

151:. In the late 1990s, researchers discovered these genes while studying cancer cells. Sometimes, 849:

Apoptosis, or programmed cell death, can occur through activation of three different pathways,

3874: 3822: 3814: 3743: 3725: 3649: 3641: 3582: 3564: 3517: 3509: 3468: 3460: 3429: 3411: 3372: 3364: 3322: 3304: 3262: 3244: 3197: 3189: 3147: 3139: 3100: 3082: 3043: 3035: 2988: 2980: 2931: 2923: 2882: 2864: 2814: 2806: 2767: 2759: 2682: 2672: 2555: 2507: 2489: 2447: 2429: 2377: 2369: 2309: 2279: 2269: 2231: 2213: 2164: 2146: 2089: 2071: 2030: 2012: 1933: 1875: 1857: 1816: 1772: 1754: 1713: 1705: 1126: 1122: 768:

of the viral RNA and protein translation. In the absence of a viral infection, E4orf4 induces

751: 1350:, specific retinal cells, and smooth muscle cells as well as in certain cancer cells such as 1238:

Organic Cation Transporter Like-3 (ORCTL3) was first discovered as a result of a large-scale

93: 3806: 3733: 3717: 3631: 3572: 3556: 3499: 3419: 3403: 3354: 3312: 3296: 3252: 3236: 3179: 3131: 3090: 3074: 3063:"The anticancer gene ORCTL3 targets stearoyl-CoA desaturase-1 for tumour-specific apoptosis" 3027: 2970: 2913: 2872: 2856: 2798: 2751: 2664: 2545: 2497: 2481: 2437: 2421: 2359: 2261: 2221: 2203: 2154: 2136: 2079: 2061: 2020: 2002: 1960: 1923: 1915: 1865: 1847: 1806: 1762: 1744: 1697: 1525: 1521: 1469: 1069: 797: 182: 3795:"Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma" 3619: 2959:"Identification of a New Urate and High Affinity Nicotinate Transporter, hOAT10 (SLC22A13)" 1509: 1200: 1145:

T Th1/Th2 cell homeostasis where in the absence of Noxa, Th2 memory T-cell death results.

974: 858: 588: 1794: 3448: 3015: 2199: 2132: 1733:"Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death" 1632:

schematic depicting the protein product via the transcription and translation of a gene.

1072:(PKR). Further studies will need to be performed to better understand the mechanisms of 541:

family and is being researched for its potential in cancer treatment and diagnosis. The

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Joyce MWATONOK, The American Cancer Society. Cancer and genes. https://www.cancer.org/.

3738: 3705: 3424: 3391: 3342: 3257: 3224: 3095: 3062: 2877: 2844: 2739: 2502: 2469: 2442: 2409: 2084: 2049: 2025: 1990: 1928: 1903: 1870: 1835: 1767: 1732: 1619: 1562: 1554: 1239: 930: 918: 887: 3577: 3544: 3317: 3284: 3135: 2902:"Identification of a kidney-specific mouse organic cation transporter like-1 (mOCTL1)" 1487: 969:

is over-expressed in normal cells, no change in growth or cell viability is detected.

3868: 3675: 3300: 3031: 2845:"Isolation of ORCTL3 in a novel genetic screen for tumor-specific apoptosis inducers" 2425: 2226: 2183: 2159: 2116: 1972: 1550: 1549:

Mutations in the p53 pathway have been observed in almost all cancer types including

1403: 1375: 1355: 1351: 1343: 1204: 1109: 946: 942: 804: 3834: 3560: 3209: 2943: 2389: 2303: 2182:

Svensson, M.; Håkansson, A.; Mossberg, A.-K.; Linse, S.; Svanborg, C. (2000-04-11).

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and its translated protein MDA-7, interacts with kinases including serine/threonine

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Irshad, S.; Mahul-Mellier, A.-L.; Kassouf, N.; Lemarie, A.; Grimm, S. (June 2009).

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Håkansson, A; Zhivotovsky, B; Orrenius, S; Sabharwal, H; Svanborg, C (1995-08-15).

1435:

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the

1399: 1312: 1192: 1161: 1092: 1029: 990: 934: 895: 862: 743: 619: 615: 186: 3636: 3359: 1622:), which exhibit various effects, such as working to prevent cancer within cells. 3168:"Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma" 2485: 2066: 1811: 1701: 796:

and E4orf4 can take advantage of this by disrupting checkpoints in mitosis. 5) A

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Toolan, H.W. (1967) Lack of oncogenic effect of the H-viruses. Nature 214, 1036.

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Proceedings of the National Academy of Sciences of the United States of America

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Proceedings of the National Academy of Sciences of the United States of America

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Zohrab, Fatemeh; Askarian, Saeedeh; Jalili, Amin; Kazemi Oskuee, Reza (2019).

1615: 1611: 1440: 1436: 1395: 1264: 1260: 1220: 961:. Multiple studies within the past 15 years have demonstrated that increasing 954: 866: 838: 781: 720: 602:

to function fully, it requires interactions with other molecules such as DNA,

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Lee, Woon Kyu; Hwang, Ji-Sun; Yun, Cheol-Heui; Cha, Seok Ho (December 2007).

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is also thought to have a pro-inflammatory purpose. It is also possible that

1008:

interacts with two of the type II cytokine hetero-dymeric receptor complexes

3343:"Inactivation of the Candidate Tumor Suppressor Par-4 in Endometrial Cancer" 2141: 1749: 1512:

lab in London. It was seen in this study that p53 could bind to viral tumor

1188: 1166: 938: 883: 769: 564: 537: 339: 258: 148: 140: 3826: 3747: 3653: 3586: 3521: 3472: 3433: 3376: 3326: 3266: 3240: 3201: 3184: 3167: 3151: 3104: 2992: 2975: 2958: 2935: 2886: 2818: 2755: 2686: 2559: 2511: 2451: 2381: 2364: 2308:. Institutet för miljömedicin (IMM) / Institute of Environmental Medicine. 2283: 2235: 2208: 2093: 2034: 1937: 1879: 1820: 1776: 1717: 3487: 3047: 2771: 2410:"mda-7/IL-24: Multifunctional cancer-specific apoptosis-inducing cytokine" 2347: 2168: 1422: 3721: 1574: 1517: 1383: 1359: 1320: 1287: 1212: 1183: 1105: 1037: 950: 788: 587:

cells, it moves to the nucleus after being activated by a process called

217: 152: 144: 3545:"Phosphorylation of Par-4 by Protein Kinase A Is Critical for Apoptosis" 3078: 2918: 2901: 2860: 2550: 2533: 1263:

exchanger in kidneys and intestine. Nicotinate is an essential vitamin (

3016:"A simple method for displaying the hydropathic character of a protein" 1607: 1513: 1444: 1299: 1293: 1179: 891: 875: 871: 777: 531:

was the first anticancer gene to be identified. It originates from the

2802: 2785:

Nishiwaki, T.; Daigo, Y.; Tamari, M.; Fujii, Y.; Nakamura, Y. (1998).

1191:. Another way that NS1 causes cytolysis is through degradation of the 2592:

Ploner, C. "Noxa: at the tip of the balance between life and death".

2330: 2007: 1686:"Anticancer genes: inducers of tumour-specific cell death signalling" 1379: 1347: 1316: 1195:

of the cell. NS1 specifically targets and degrades the microfilament

1138: 1134: 1052:, be involved in signaling short-range, and immune function in skin. 567:. This difference allows apoptin to selectively target cancer cells. 174: 1991:"Mechanisms of Cancer Cell Killing by the Adenovirus E4orf4 Protein" 1731:

Wyatt, Jasmine; Müller, Manuel M.; Tavassoli, Mahvash (2019-12-07).

2348:"HAMLET Interacts with Histones and Chromatin in Tumor Cell Nuclei" 1282:. ORCTL3 has been shown to be activated for apoptosis induction in 857:. HAMLET proceeds by both a multifaceted intrinsic pathway and the 1624: 1415: 1370: 1279: 1247: 1130: 684: 480: 212: 1472:

leading to apoptosis, while in the other the complex activates a

3676:"The Discovery of p53 Protein | The Embryo Project Encyclopedia" 3392:"Tumour-suppression activity of the proapoptotic regulator Par4" 1603: 1530: 1339: 607: 452: 372: 1625: 1271:

synthesis, which in turn is important for energetic processes,

1501: 773: 624: 205: 29: 3120:"Apoptosis by Par-4 in cancer and neurodegenerative diseases" 2184:"Conversion of α-lactalbumin to a protein inducing apoptosis" 1799:

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

1012:

and IL-22R1/IL-20R2. It has been seen that in some contexts,

894:, double-membrane vesicles, and a dose-dependent decrease in 2470:"MDA-7/IL-24 as a cancer therapeutic: from bench to bedside" 2332:

HAMLET - In vivo effects and mechanisms of tumor-cell death

723:

at the G2/M phase, resulting in an induction of apoptosis.

1953:

International Journal of Peptide Research and Therapeutics

1908:

International Journal of Peptide Research and Therapeutics

535:(CAV), which has circular DNA. This virus belongs to the 3620:"Targeting TRAIL Agonistic Receptors for Cancer Therapy" 1112:. In humans, the Noxa homologue is known as APR/PMAIP1. 645: 3488:"Oncogenic Ras Sensitizes Cells to Apoptosis by Par-4" 719:

to prevent the progression of cancer by arresting the

185:

varies depending on its type and how advanced it is.

1275:

pathways, and the activation of the NAD+ -dependent

3118:El-Guendy, Nadia; Rangnekar, Vivek M (2003-02-01). 742:Early region 4 open-reading-frame 4 (E4orf4) is an 640:

may be too technical for most readers to understand

60:. Unsourced material may be challenged and removed. 3761: 3759: 3757: 1984: 1982: 1223:occurs, which in this case results in cell death. 3706:"Mechanisms of transcriptional regulation by p53" 3278: 3276: 2838: 2836: 1315:. The fact that SCD is commonly overexpressed in 941:. Protein structural studies reveal that it is a 823:Crystal Structure of Calcium-bound α-lactalbumin. 3014:Kyte, Jack; Doolittle, Russell F. (1982-05-05). 2247: 2245: 1684:Grimm, Stefan; Noteborn, Mathieu (2010-02-01). 2654: 2652: 1455:that can also be cleaved into a soluble form. 2527: 2525: 2523: 2521: 2403: 2401: 2399: 1500:TP-53 is a gene that encodes for the protein 1219:, causing DNA damage. When DNA is damaged, a 1091:Noxa, isolated from mice, is a member of the 8: 2463: 2461: 913:Melanoma differentiation associated gene-7 ( 890:. This includes the presence of cytoplasmic 2117:"Apoptosis induced by a human milk protein" 1840:Frontiers in Cell and Developmental Biology 591:. This movement is triggered by the enzyme 3788: 3786: 1788: 1786: 1667:BMC Complementary and Alternative Medicine 1660: 1658: 1303:. For its apoptosis effect ORCTL3 targets 1189:caspase 3/9-mediated programmed cell death 135:have a special ability to target and kill 3737: 3635: 3576: 3503: 3423: 3358: 3316: 3256: 3183: 3094: 2974: 2917: 2876: 2587: 2585: 2583: 2581: 2579: 2577: 2549: 2501: 2441: 2363: 2335:(thesis/doccomp thesis). Lund University. 2225: 2207: 2158: 2140: 2083: 2065: 2024: 2006: 1927: 1869: 1851: 1810: 1766: 1748: 1060:induces cytokine secretion, which causes 937:), and the shared properties it has with 668:Learn how and when to remove this message 652:, without removing the technical details. 229:Subcellular localization in cancer cells 120:Learn how and when to remove this message 1897: 1895: 1893: 1891: 1889: 1486: 1421: 1028:can be placed into tumor cell lines via 921:, was discovered in the mid-1900s using 818: 197: 1654: 1466:death-inducing signaling complex (DISC) 3699: 3697: 3695: 1259:identified as the first high-affinity 2906:Experimental & Molecular Medicine 1610:they code for. Genes are composed of 1571:head and neck squamous cell carcinoma 1382:, inhibition of apoptosis, increased 650:make it understandable to non-experts 7: 58:adding citations to reliable sources 1795:"Apoptin, a tumor-selective killer" 1508:and technician Alan K. Roberts, in 1307:(SCD), an enzyme that introduces a 1024:cell growth arrest and cell death. 595:at a specific site on the protein. 1437:tumor necrosis factor (TNF) family 25: 3767:"TP53 gene: MedlinePlus Genetics" 1989:Kleinberger, Tamar (2015-05-07). 1614:, while proteins are composed of 1426:Crystal Structure of Human TRAIL. 929:is classified in the interleukin 618:, with potential applications in 3710:Cell Death & Differentiation 3301:10.1128/MCB.23.16.5516-5525.2003 2849:Cell Death & Differentiation 2426:10.1016/j.pharmthera.2005.11.005 1544:post-translational modifications 977:cytokine because it generates a 629: 164:Anticancer genes as therapeutics 34: 27:Type of gene used for anticancer 3561:10.1128/MCB.25.3.1146-1161.2005 3492:Journal of Biological Chemistry 2963:Journal of Biological Chemistry 2791:Cytogenetic and Genome Research 2414:Pharmacology & Therapeutics 2352:Journal of Biological Chemistry 1491:Structure of TP53 bound to DNA. 1338:Prostate apoptosis response-4 ( 1209:actin-severing protein gelsolin 878:leading to the inactivation of 874:. HAMLET irreversibly binds to 512:Common anticancer gene examples 45:needs additional citations for 3549:Molecular and Cellular Biology 3289:Molecular and Cellular Biology 2302:Köhler, Camilla (2001-11-23). 1520:. This later study was run by 1: 3637:10.1158/1078-0432.CCR-06-2774 3360:10.1158/0008-5472.CAN-06-2687 3136:10.1016/S0014-4827(02)00016-2 472:Nucleus, ER, plasma membrane 223:Activated by phosphorylation 3032:10.1016/0022-2836(82)90515-0 3020:Journal of Molecular Biology 2486:10.1097/CAD.0b013e32833cfbe1 2258:Bioactive Components of Milk 2067:10.1371/journal.ppat.1005420 1812:10.1016/j.bbamcr.2009.04.002 1702:10.1016/j.molmed.2009.12.002 1690:Trends in Molecular Medicine 1102:chronic lymphocytic leukemia 226:Engaging cell death pathway 143:, and other mechanisms like 2669:10.1007/978-1-4471-6458-6_5 2266:10.1007/978-0-387-74087-4_8 1244:organic cation transporters 1048:could potentially act as a 444:Plasma membrane, ER, golgi 194:Summary of anticancer genes 3896: 3124:Experimental Cell Research 2329:Gustafsson, Lotta (2005). 1965:10.1007/s10989-019-09903-6 335:Nucleus, ER, mitochondria 167: 3811:10.1007/s13277-013-0736-9 3229:British Journal of Cancer 1920:10.1007/s10989-018-9723-8 957:, compared to normal non- 923:subtraction hybridization 638:This rest of the article 3624:Clinical Cancer Research 3505:10.1074/jbc.274.42.29976 3408:10.1038/sj.embor.7400421 2744:Human Molecular Genetics 1853:10.3389/fcell.2020.00524 1453:type II membrane protein 1386:activity, and decreased 1062:antigen-presenting cells 935:human chromosome 1q32-33 570:Research has shown that 2142:10.1073/pnas.92.17.8064 1750:10.3390/cancers11121975 1402:, respectively, to the 1305:stearoyl-CoA desaturase 1217:reactive oxygen species 1108:found in adults in the 1104:(CLL), the most common 979:reactive oxygen species 549:in human cancer cells. 170:Gene therapy for cancer 3241:10.1054/bjoc.2001.2158 3185:10.1038/sj.onc.1202416 2976:10.1074/jbc.M800737200 2365:10.1074/jbc.M306462200 2209:10.1073/pnas.97.8.4221 1643:Tumour suppressor gene 1633: 1606:are confused with the 1492: 1427: 1267:) that is involved in 1207:through activation of 824: 794:cell cycle checkpoints 748:protein phosphatase 2A 694: 3859:Genes, DNA and Cancer 1628: 1598:Common misconceptions 1490: 1425: 1125:induced apoptosis. A 1098:adult T-cell leukemia 983:endoplasmic reticulum 981:and causes stress in 973:is also considered a 917:), and also known as 855:tumor necrosis factor 822: 688: 612:Lewis lung carcinomas 547:programmed cell death 469:Extrinsic, Intrinsic 364:Receptor-binding, ER 3857:Cancer Research UK. 3722:10.1038/cdd.2017.174 2756:10.1093/hmg/3.8.1341 1589:BRCA gene mutations: 1583:soft tissue sarcomas 1510:Lionel V. Crawford's 1160:In the 1960s rodent 766:alternative splicing 704:Rana brevipoda porsa 533:Chicken Anemia Virus 312:Mitotic catastrophe 183:treatment for cancer 54:improve this article 3498:(42): 29976–29983. 3079:10.1038/onc.2014.93 2969:(24): 16332–16341. 2919:10.1038/emm.2007.85 2861:10.1038/cdd.2009.21 2551:10.1038/cgt.2012.84 2532:Zhang, L-N (2013). 2358:(43): 42131–42135. 2200:2000PNAS...97.4221S 2133:1995PNAS...92.8064H 1522:Daniel I. H. Linzer 1439:that also includes 1277:histone deacetylase 1273:signal transduction 1221:DNA damage response 782:DNA damage response 702:Skin from the frog 559:. In cancer cells, 309:Nucleus, cytoplasm 232:Type of cell death 1634: 1567:cholangiocarcinoma 1493: 1428: 1344:chromosome 12q21.2 1311:in the fatty acid 1129:gene found in the 955:metastatic disease 825: 708:Pelophylax porosus 695: 3459:(19): 7255–7263. 3295:(16): 5516–5525. 3235:(11): 1801–1808. 3073:(13): 1718–1728. 2803:10.1159/000015197 2678:978-1-4471-6457-9 2474:Anti-Cancer Drugs 2315:978-91-7349-048-1 2275:978-0-387-74087-4 2127:(17): 8064–8068. 1506:David Philip Lane 975:radio-sensitizing 959:transformed cells 678: 677: 670: 507: 506: 500:Receptor-binding 201:Anti-cancer gene 130: 129: 122: 104: 69:"Anticancer gene" 16:(Redirected from 3887: 3880:Anticancer genes 3839: 3838: 3805:(3): 1919–1923. 3790: 3781: 3780: 3778: 3777: 3763: 3752: 3751: 3741: 3701: 3690: 3689: 3687: 3686: 3672: 3666: 3665: 3639: 3630:(8): 2313–2317. 3615: 3609: 3606: 3600: 3597: 3591: 3590: 3580: 3555:(3): 1146–1161. 3540: 3534: 3533: 3507: 3483: 3477: 3476: 3444: 3438: 3437: 3427: 3387: 3381: 3380: 3362: 3353:(5): 1927–1934. 3337: 3331: 3330: 3320: 3280: 3271: 3270: 3260: 3220: 3214: 3213: 3187: 3178:(5): 1205–1208. 3162: 3156: 3155: 3115: 3109: 3108: 3098: 3058: 3052: 3051: 3011: 3005: 3004: 2978: 2954: 2948: 2947: 2921: 2897: 2891: 2890: 2880: 2840: 2831: 2830: 2797:(3–4): 251–255. 2782: 2776: 2775: 2750:(8): 1341–1344. 2734: 2728: 2725: 2719: 2716: 2710: 2707: 2701: 2697: 2691: 2690: 2661:Anticancer Genes 2656: 2647: 2644: 2638: 2635: 2629: 2626: 2620: 2617: 2611: 2608: 2602: 2601: 2589: 2572: 2571: 2553: 2529: 2516: 2515: 2505: 2465: 2456: 2455: 2445: 2405: 2394: 2393: 2367: 2343: 2337: 2336: 2326: 2320: 2319: 2299: 2293: 2292: 2291: 2290: 2249: 2240: 2239: 2229: 2211: 2194:(8): 4221–4226. 2179: 2173: 2172: 2162: 2144: 2112: 2106: 2105: 2087: 2069: 2045: 2039: 2038: 2028: 2010: 2008:10.3390/v7052334 2001:(5): 2334–2357. 1986: 1977: 1976: 1959:(2): 1013–1020. 1948: 1942: 1941: 1931: 1899: 1884: 1883: 1873: 1855: 1831: 1825: 1824: 1814: 1805:(8): 1335–1342. 1790: 1781: 1780: 1770: 1752: 1728: 1722: 1721: 1681: 1675: 1674: 1662: 1526:Arnold J. Levine 1470:effector caspase 1408:protein kinase A 1201:casein kinase II 1050:paracrine factor 853:, extrinsic, or 673: 666: 662: 659: 653: 633: 632: 625: 198: 133:Anticancer genes 125: 118: 114: 111: 105: 103: 62: 38: 30: 21: 18:Anticancer genes 3895: 3894: 3890: 3889: 3888: 3886: 3885: 3884: 3865: 3864: 3848: 3846:Further reading 3843: 3842: 3792: 3791: 3784: 3775: 3773: 3771:medlineplus.gov 3765: 3764: 3755: 3703: 3702: 3693: 3684: 3682: 3674: 3673: 3669: 3617: 3616: 3612: 3607: 3603: 3598: 3594: 3542: 3541: 3537: 3485: 3484: 3480: 3453:Cancer Research 3446: 3445: 3441: 3389: 3388: 3384: 3347:Cancer Research 3339: 3338: 3334: 3282: 3281: 3274: 3222: 3221: 3217: 3164: 3163: 3159: 3117: 3116: 3112: 3060: 3059: 3055: 3013: 3012: 3008: 2956: 2955: 2951: 2899: 2898: 2894: 2842: 2841: 2834: 2784: 2783: 2779: 2736: 2735: 2731: 2726: 2722: 2717: 2713: 2708: 2704: 2698: 2694: 2679: 2658: 2657: 2650: 2645: 2641: 2636: 2632: 2627: 2623: 2618: 2614: 2609: 2605: 2591: 2590: 2575: 2531: 2530: 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1518:antibodies 1265:Vitamin B3 1261:nicotinate 1162:parvovirus 1016:activates 839:oleic acid 799:Drosophila 744:adenovirus 721:cell cycle 503:Apoptosis 497:Extrinsic 475:Apoptosis 447:Apoptosis 441:Intrinsic 421:Apoptosis 418:Cytoplasm 415:Intrinsic 395:Apoptosis 389:Intrinsic 367:Apoptosis 361:Intrinsic 332:Intrinsic 306:Intrinsic 286:Autophagy 283:Cytoplasm 280:Intrinsic 252:Intrinsic 80:newspapers 3819:1010-4283 3730:1476-5403 3646:1078-0432 3569:0270-7306 3514:0021-9258 3465:0008-5472 3416:1469-221X 3369:0008-5472 3309:0270-7306 3249:1532-1827 3194:1476-5594 3144:0014-4827 3087:1476-5594 3040:0022-2836 2985:0021-9258 2928:2092-6413 2869:1476-5403 2811:1424-8581 2764:0964-6906 2494:0959-4973 2434:0163-7258 2374:0021-9258 2218:0027-8424 2151:0027-8424 2076:1553-7374 2017:1999-4915 1973:199407384 1862:2296-634X 1759:2072-6694 1710:1471-4914 1167:cytolysis 939:cytokines 884:chromatin 851:intrinsic 789:oncogenic 770:apoptosis 755:to bind. 565:cytoplasm 538:Gyrovirus 340:autophagy 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3001:5522658 2878:2683172 2827:9118091 2772:7987312 2568:7183342 2503:2915543 2443:1781515 2196:Bibcode 2169:7644538 2129:Bibcode 2085:4750969 2026:4452909 1995:Viruses 1929:7087712 1871:7330108 1846:: 524. 1768:6966515 1737:Cancers 1673:: 1–11. 1602:Often, 1496:History 1431:History 1380:T cells 1348:neurons 1334:History 1300:ex vivo 1294:in vivo 1234:History 1156:History 1123:hypoxia 1087:History 909:History 828:History 778:caspase 738:History 644:Please 600:apoptin 584:Apoptin 572:apoptin 561:apoptin 553:Apoptin 543:apoptin 529:Apoptin 524:History 518:APOPTIN 426:ORCTL3 317:HAMLET 291:E4orf4 94:scholar 3833: 3825: 3817: 3746: 3736: 3728: 3660: 3652: 3644: 3585: 3578:544017 3575: 3567: 3528: 3520: 3512: 3471: 3463: 3432: 3422: 3414: 3375: 3367: 3325: 3318:166354 3315: 3307: 3265: 3255: 3247: 3208: 3200: 3192: 3150: 3142: 3103: 3093: 3085: 3046: 3038: 2999: 2991: 2983: 2942: 2934: 2926: 2885: 2875: 2867: 2825: 2817: 2809: 2770: 2762: 2685: 2675: 2594:Nature 2566: 2558: 2538:Nature 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