196:, often located at the cell's surface imbedded in the plasma membrane. When such signals interact with a receptor, they effectively direct the cell to do something, such as dividing, dying, or allowing substances to be created, or to enter or exit the cell. A cell's ability to respond to a chemical message depends on the presence of receptors tuned to that message. The more receptors a cell has that are tuned to the message, the more the cell will respond to it.
280:. The internalization of the insulin molecules provides a pathway for degradation of the hormone, as well as for regulation of the number of sites that are available for binding on the cell surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of
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levels. The near-constant increase in blood insulin levels results from an effort to match the increase in blood glucose, which will cause receptor sites on the liver cells to downregulate and decrease the number of receptors for insulin, increasing the subject's resistance by decreasing sensitivity
199:
Receptors are created, or expressed, from instructions in the DNA of the cell, and they can be increased, or upregulated, when the signal is weak, or decreased, or downregulated, when it is strong. Their level can also be up or down regulated by modulation of systems that degrade receptors when they
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Taken together, our data suggest that normal repair of a DNA break can occasionally cause heritable silencing of a CpG island–containing promoter by recruitment of proteins involved in silencing...This finding suggests that DNA damage may directly contribute to the large number of epigenetically
215:-induced desensitization or internalization of that receptor. This is typically seen in animal hormone receptors. Upregulation of receptors, on the other hand, can result in super-sensitized cells, especially after repeated exposure to an antagonistic drug or prolonged absence of the ligand.
1049:
Cuozzo, Concetta; Porcellini, Antonio; Angrisano, Tiziana; Morano, Annalisa; Lee, Bongyong; Pardo, Alba Di; Messina, Samantha; Iuliano, Rodolfo; Fusco, Alfredo; Santillo, Maria R; Muller, Mark T; Chiariotti, Lorenzo; Gottesman, Max E; Avvedimento, Enrico V (6 July 2007).
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and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell's sensitivity to the elevated hormone concentration.
1302:
Mego, Michal; Cierna, Zuzana; Svetlovska, Daniela; Macak, Dusan; Machalekova, Katarina; Miskovska, Viera; Chovanec, Michal; Usakova, Vanda; Obertova, Jana; Babal, Pavel; Mardiak, Jozef (July 2013). "PARP expression in germ cell tumours".
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Especially among genetically vulnerable individuals, repeated exposure to a drug of abuse in adolescence or adulthood causes addiction by inducing stable downregulation or upregulation in expression of specific genes and
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Newman, Robert; Soldatenkov, Viatcheslav; Dritschilo, Anatoly; Notario, Vicente (1 May 2002). "Poly(ADP-ribose) polymerase turnover alterations do not contribute to PARP overexpression in Ewing's sarcoma cells".
1904:
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occurs in 93% of bladder cancers, 88% of stomach cancers, 74% of thyroid cancers, 40–90% of colorectal cancers, and 50% of brain cancers. Similarly, epigenetic downregulation of
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Muvarak, Nidal; Kelley, Shannon; Robert, Carine; Baer, Maria R.; Perrotti, Danilo; Gambacorti-Passerini, Carlo; Civin, Curt; Scheibner, Kara; Rassool, Feyruz V. (1 April 2015).
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in the blood trigger downregulation of the associated receptors. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes
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alteration. Such an epigenetic alteration can cause expression of the RNA or protein to no longer respond to an external stimulus. This occurs, for instance, during
394:). Investigation of epigenetic down- or upregulation of repaired DNA genes as possibly central to progression of cancer has been regularly undertaken since 2000.
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Family-based, adoption, and twin studies have indicated that there is a strong (50%) heritable component to vulnerability to substance abuse addiction.
1092:...data support a mechanistic link between HR and DNA methylation and suggest that DNA methylation in eukaryotes marks homologous recombined segments.
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All living cells have the ability to receive and process signals that originate outside their membranes, which they do by means of proteins called
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1208:"c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase–Activated Leukemias"
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is over-expressed in tyrosine kinase-activated leukemias, in neuroblastoma, in testicular and other germ cell tumors, and in Ewing's sarcoma.
1157:"Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer"
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Downregulation of receptors can also occur when receptors have been chronically exposed to an excessive amount of a ligand, either from
70:, in response to an external stimulus. The complementary process that involves increase in quantities of cellular components is called
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993:"Double Strand Breaks Can Initiate Gene Silencing and SIRT1-Dependent Onset of DNA Methylation in an Exogenous Promoter CpG Island"
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Bernstein, C; Prasad, AR; Nfonsam, V; Bernstein, H. (2013). "Chapter 16: DNA Damage, DNA Repair and Cancer". In Chen, Clark (ed.).
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Zaliauskiene, Lolita; Kang, Sunghyun; Brouillette, Christie G.; Lebowitz, Jacob; Arani, Ramin B.; Collawn, James F. (2016).
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Newman, Erika A.; Lu, Fujia; Bashllari, Daniela; Wang, Li; Opipari, Anthony W.; Castle, Valerie P. (1 March 2015).
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is upregulated in the majority of cancers of the breast, prostate, stomach, neuroblastomas, pancreas, and lung.
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temporarily upregulate their respective receptors. The disequilibrium caused by these changes often causes
606:"Down-Regulation of Cell Surface Receptors Is Modulated by Polar Residues within the Transmembrane Domain"
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364:. Such downregulation or upregulation has been shown to occur in the brain's reward regions, such as the
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alterations due to errors during DNA repair. Such mutations and epigenetic alterations can give rise to
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742:"Alterations of insulin signaling in type 2 diabetes: A review of the current evidence from humans"
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565:"On the mechanism of ligand-induced down-regulation of insulin receptor level in the liver cell"
88:, which reduces the cell's sensitivity to the molecule. This is an example of a locally acting (
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DNA damage appears to be the primary underlying cause of cancer. DNA damage can also increase
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in the liver even when blood glucose levels are elevated. This is the more common process of
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663:"Insulin receptor internalization: molecular mechanisms and physiopathological implications"
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1257:"Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma"
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Bilgrami, Shumaila M; Qureshi, Sohail A; Pervez, Shahid; Abbas, Farhat (December 2014).
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An example of downregulation is the cellular decrease in the expression of a specific
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454:. If this pathway is upregulated, the excess mutations it causes can lead to cancer.
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1384:"Chemical-induced cancer incidence and underlying mechanisms in Fen1 mutant mice"
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must release more insulin than normal to meet the demand and return the blood to
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Baxter, Eva; Windloch, Karolina; Gannon, Frank; Lee, Jason S (December 2014).
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O'Hagan, Heather M.; Mohammad, Helai P.; Baylin, Stephen B. (15 August 2008).
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Walker, Deena M.; Nestler, Eric J. (2018). "Neuroepigenetics and addiction".
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receptor sites on target cells, e.g. liver cells, in a person with type 2
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Downregulation or upregulation of an RNA or protein may also arise by an
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are essential genes in the error-prone and mutagenic DNA repair pathway
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occurs in 82% of colorectal cancers and epigenetic downregulation of
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to this hormone. There is also a hepatic decrease in sensitivity to
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may cause downregulation of their respective receptors, while most
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Sherwood, Lauralee; Klandorf, Hillar; Yancey, Paul (2012-01-01).
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Upregulation and downregulation can also happen as a response to
111:, which in turn increases degradation of these dioxin molecules.
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in response to its increased activation by a molecule, such as a
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Biochimica et
Biophysica Acta (BBA) - Molecular Basis of Disease
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107:. In this situation, the cells increase their production of
1052:"DNA Damage, Homology-Directed Repair, and DNA Methylation"
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Fröjdö, Sara; Vidal, Hubert; Pirola, Luciano (2009-02-01).
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Xu, H; Zheng, L; Dai, H; Zhou, M; Hua, Y; Shen, B (2011).
506:"Regulation of Gene Expression in the Genomic Context"
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510:Computational and Structural Biotechnology Journal
504:Atkinson, Taylor J; Halfon, Marc S (2014-01-01).
397:Epigenetic downregulation of the DNA repair gene
426:Epigenetic upregulation of the DNA repair genes
58:decreases the production and quantities of its
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273:and is subsequently attacked by intracellular
95:An example of upregulation is the response of
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1106:"Epigenetic regulation in cancer progression"
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340:, in which the kidneys become insensitive to
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130:Downregulation and upregulation of receptors
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716:Animal Physiology: From Genes to Organisms
1437:at the U.S. National Library of Medicine
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920:"Epigenetic mechanisms of drug addiction"
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180:Learn how and when to remove this message
261:Example: Insulin receptor downregulation
563:Krupp, M; Lane, MD (25 February 1981).
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333:, which leads to adult-onset diabetes.
967:. BoD – Books on Demand. p. 413.
300:. Due to the elevated levels of blood
965:New Research Directions in DNA Repair
440:Regulation of transcription in cancer
378:Regulation of transcription in cancer
325:. This can be seen in the continuing
200:are no longer required by the cell.
7:
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249:is hormones that cause cells in the
162:adding citations to reliable sources
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868:. Vol. 148. pp. 747–765.
832:"Protein Controversies in Diabetes"
569:The Journal of Biological Chemistry
292:This process is illustrated by the
874:10.1016/B978-0-444-64076-5.00048-X
452:microhomology-mediated end joining
25:
1743:Post-transcriptional modification
918:Nestler, Eric J. (January 2014).
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1887:
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932:10.1016/j.neuropharm.2013.04.004
783:"Insulin and Insulin Resistance"
438:occurs in numerous cancers (see
245:. An example of upregulation in
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1748:Post-translational modification
336:Another example can be seen in
265:Elevated levels of the hormone
149:needs additional citations for
866:Handbook of Clinical Neurology
1:
1870:Post-translational regulation
1317:10.1136/jclinpath-2012-201088
1305:Journal of Clinical Pathology
1273:10.1158/1541-7786.MCR-14-0337
1224:10.1158/1541-7786.MCR-14-0422
781:Wilcox, Gisela (2016-11-20).
610:Molecular Biology of the Cell
582:10.1016/S0021-9258(19)69862-5
472:Regulation of gene expression
44:regulation of gene expression
1818:High-throughput technique ("
1069:10.1371/journal.pgen.0030110
1010:10.1371/journal.pgen.1000155
759:10.1016/j.bbadis.2008.10.019
284:of new receptors within the
253:to become more sensitive to
230:when the long-term use of a
1696:Functional biology/medicine
787:Clinical Biochemist Reviews
421:non-small-cell lung cancers
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661:Carpentier, J.-L. (1994).
477:Transcriptional regulation
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54:is the process by which a
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1261:Molecular Cancer Research
1212:Molecular Cancer Research
1034:silenced genes in tumors.
830:Franz, Marion J. (2000).
1439:Medical Subject Headings
1174:10.1186/2193-1801-3-178
211:drugs. This results in
109:cytochrome P450 enzymes
1123:10.1186/2045-3701-4-45
523:10.5936/csbj.201401001
362:epigenetic alterations
304:in an individual, the
99:cells exposed to such
1691:Developmental biology
1686:Computational biology
1110:Cell & Bioscience
622:10.1091/mbc.11.8.2643
417:head and neck cancers
286:endoplasmic reticulum
124:progression to cancer
1865:Post-transcriptional
1400:10.1038/onc.2010.482
719:. Cengage Learning.
342:arginine vasopressin
310:islets of Langerhans
224:receptor antagonists
158:improve this article
27:Biological processes
1660:Histone methylation
926:. 76 Pt B: 259–68.
842:(3). Archived from
482:Enhancer (genetics)
392:malignant neoplasms
60:cellular components
1361:10.3892/or.9.3.529
680:10.1007/BF00400835
516:(13): e201401001.
338:diabetes insipidus
331:insulin resistance
207:mediators or from
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1893:Molecular biology
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1832:Mass spectrometry
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1476:Molecular biology
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924:Neuropharmacology
836:Diabetes Spectrum
415:occurs in 62% of
366:nucleus accumbens
234:is discontinued.
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48:gene products
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1937:Cell biology
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1803:Fluorescence
1791:Nucleic acid
1782:C57BL/6 mice
1773:Cell culture
1681:Biochemistry
1676:Cell biology
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156:Please help
151:verification
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32:biochemistry
29:
1905:WikiProject
1714:Engineering
1669:Linked life
1584:Pribnow box
1542:Translation
1062:(7): e110.
318:homeostatic
271:endocytosis
38:context of
1921:Categories
1855:Epigenetic
1766:Techniques
1628:Terminator
1611:trp operon
1606:lac operon
1601:gal operon
1167:(1): 178.
850:2016-11-20
491:References
384:epigenetic
376:See also:
228:withdrawal
205:endogenous
116:epigenetic
101:xenobiotic
62:, such as
36:biological
18:Upregulate
1780:(such as
1638:Repressor
1116:(1): 45.
799:0159-8090
689:0012-186X
630:1059-1524
532:2001-0370
358:microRNAs
312:) in the
282:synthesis
275:lysosomal
247:pregnancy
209:exogenous
194:receptors
40:organisms
34:, in the
1932:Genetics
1787:Methods
1721:Concepts
1701:Genetics
1655:Silencer
1633:Enhancer
1589:TATA box
1579:Promoter
1570:Heredity
1506:Overview
1497:Glossary
1418:20972458
1388:Oncogene
1369:11956622
1325:23486608
1281:25563294
1242:25828893
1193:24790823
1142:25949794
1088:17616978
1029:18704159
950:23643695
902:29478612
817:16278749
768:19041393
648:10930460
550:24688749
466:See also
360:through
314:pancreas
298:diabetes
255:oxytocin
243:hormones
78:receptor
68:proteins
1860:Genetic
1807:Pigment
1796:Protein
1757:Wet lab
1753:Dry lab
1733:Mitosis
1565:Genetic
1556:Element
1546:protein
1487:History
1409:3832200
1289:1830505
1233:4398615
1184:4000596
1133:4422217
1079:1913100
1020:2491723
941:3766384
893:5868351
808:1204764
697:7821727
591:7007369
541:3962188
323:insulin
306:β-cells
302:glucose
294:insulin
278:enzymes
267:insulin
82:hormone
1820:-omics
1809:&
1618:Intron
1596:Operon
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251:uterus
239:toxins
213:ligand
105:dioxin
1492:Index
1329:S2CID
1285:S2CID
639:14946
456:PARP1
444:PARP1
429:PARP1
412:NEIL1
390:(see
218:Some
97:liver
1623:Exon
1414:PMID
1365:PMID
1321:PMID
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969:ISBN
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685:ISSN
644:PMID
626:ISSN
587:PMID
546:PMID
528:ISSN
460:FEN1
448:FEN1
446:and
435:FEN1
432:and
406:LIG4
400:MGMT
232:drug
66:and
56:cell
1536:RNA
1526:DNA
1404:PMC
1396:doi
1357:doi
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888:PMC
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634:PMC
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