Editing Notch signaling pathway (section)

{{Short description|Series of molecular signals}}
[[File:Notchccr.svg|thumb|Notch-mediated [[Juxtacrine signalling|juxtacrine signal]] between adjacent cells]]
[[File:Notch signaling.svg|thumb|Notch signaling steps]]

The '''Notch signaling pathway''' is a highly [[Conserved sequence|conserved]] [[cell signaling]] system present in most [[animal|animals]].<ref name="pmid10221902">{{cite journal | vauthors = Artavanis-Tsakonas S, Rand MD, Lake RJ | title = Notch signaling: cell fate control and signal integration in development | journal = Science | volume = 284 | issue = 5415 | pages = 770–776 | date = April 1999 | pmid = 10221902 | doi = 10.1126/science.284.5415.770 | bibcode = 1999Sci...284..770A }}</ref> Mammals possess four different [[Notch proteins|notch receptors]], referred to as [[NOTCH1]], [[NOTCH2]], [[Notch 3|NOTCH3]], and [[NOTCH4]].<ref name="ReferenceB">{{cite journal | vauthors = Kumar R, Juillerat-Jeanneret L, Golshayan D | title = Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases | journal = Journal of Medicinal Chemistry | volume = 59 | issue = 17 | pages = 7719–7737 | date = September 2016 | pmid = 27045975 | doi = 10.1021/acs.jmedchem.5b01516 | s2cid = 43654713 | url = https://figshare.com/articles/journal_contribution/7928825 }}</ref> The notch receptor is a single-pass [[Cell surface receptor|transmembrane receptor]] protein. It is a [[hetero-oligomer]] composed of a large [[extracellular]] portion, which associates in a [[calcium]]-dependent, [[non-covalent]] interaction with a smaller piece of the notch protein composed of a short extracellular region, a single transmembrane-pass, and a small [[intracellular]] region.<ref name="pmid10882063">{{cite journal | vauthors = Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, Cumano A, Roux P, Black RA, Israël A | display-authors = 6 | title = A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE | journal = Molecular Cell | volume = 5 | issue = 2 | pages = 207–216 | date = February 2000 | pmid = 10882063 | doi = 10.1016/S1097-2765(00)80417-7 | doi-access = free }}</ref>

Notch signaling promotes proliferative signaling during [[neurogenesis]], and its activity is inhibited by [[NUMB (gene)|Numb]] to promote neural differentiation. It plays a major role in the regulation of embryonic development. 

Notch signaling is dysregulated in many cancers, and faulty notch signaling is implicated in many diseases, including T-cell acute lymphoblastic leukemia ([[Precursor T acute lymphoblastic leukemia/lymphoma|T-ALL]]),<ref name="pmid17404512">{{cite journal | vauthors = Sharma VM, Draheim KM, Kelliher MA | title = The Notch1/c-Myc pathway in T cell leukemia | journal = Cell Cycle | volume = 6 | issue = 8 | pages = 927–930 | date = April 2007 | pmid = 17404512 | doi = 10.4161/cc.6.8.4134 | doi-access = free }}</ref> cerebral autosomal-dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL), multiple sclerosis, [[Tetralogy of Fallot]], and [[Alagille syndrome]]. Inhibition of notch signaling inhibits the proliferation of T-cell acute lymphoblastic leukemia in both cultured cells and a mouse model.<ref>{{cite journal | vauthors = Moellering RE, Cornejo M, Davis TN, Del Bianco C, Aster JC, Blacklow SC, Kung AL, Gilliland DG, Verdine GL, Bradner JE | display-authors = 6 | title = Direct inhibition of the NOTCH transcription factor complex | journal = Nature | volume = 462 | issue = 7270 | pages = 182–188 | date = November 2009 | pmid = 19907488 | pmc = 2951323 | doi = 10.1038/nature08543 | bibcode = 2009Natur.462..182M }}</ref><ref>{{cite journal | vauthors = Arora PS, Ansari AZ | title = Chemical biology: A Notch above other inhibitors | journal = Nature | volume = 462 | issue = 7270 | pages = 171–173 | date = November 2009 | pmid = 19907487 | doi = 10.1038/462171a | s2cid = 205050842 | doi-access = free | bibcode = 2009Natur.462..171A }}</ref>