Notch 1 Explained

Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the NOTCH1 gene.[1] Notch 1 is a single-pass transmembrane receptor.

Function

This gene encodes a member of the Notch family. Members of this type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in humans, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play multiple roles during development.[2]

A deficiency can be associated with bicuspid aortic valve.[3]

There is evidence that activated Notch 1 and Notch 3 promote differentiation of progenitor cells into astroglia.[4] Notch 1, when activated before birth, induces radial glia differentiation,[5] but postnatally induces the differentiation into astrocytes.[6] One study shows that Notch-1 cascade is activated by Reelin in an unidentified way.[7] Reelin and Notch1 cooperate in the development of the dentate gyrus, according to another.[8]

Interactions

NOTCH1 has been shown to interact with:

Further reading

External links

Notes and References

  1. Web site: NOTCH1 - Neurogenic locus notch homolog protein 1 precursor - Homo sapiens (Human) - NOTCH1 gene & protein . www.uniprot.org . 23 May 2022 . en.
  2. Web site: Entrez Gene: NOTCH1 Notch homolog 1, translocation-associated (Drosophila).
  3. McKellar SH, Tester DJ, Yagubyan M, Majumdar R, Ackerman MJ, Sundt TM . Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms . . 134 . 2 . 290–296 . August 2007 . 17662764 . 10.1016/j.jtcvs.2007.02.041 . free .
  4. Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T . Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate . . 29 . 1 . 45–55 . January 2001 . 11182080 . 10.1016/S0896-6273(01)00179-9 . 2433/150564 . 17047028 . free .
  5. Gaiano N, Nye JS, Fishell G . Radial glial identity is promoted by Notch1 signaling in the murine forebrain . . 26 . 2 . 395–404 . May 2000 . 10839358 . 10.1016/S0896-6273(00)81172-1 . 15861936 . free .
  6. Chambers CB, Peng Y, Nguyen H, Gaiano N, Fishell G, Nye JS . Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors . . 128 . 5 . 689–702 . March 2001 . 10.1242/dev.128.5.689 . 11171394 .
  7. Keilani S, Sugaya K . Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-1 . . 8 . 1 . 69 . July 2008 . 18593473 . 2447831 . 10.1186/1471-213X-8-69 . free .
  8. Sibbe M, Förster E, Basak O, Taylor V, Frotscher M . Reelin and Notch1 cooperate in the development of the dentate gyrus . . 29 . 26 . 8578–85 . July 2009 . 19571148 . 6665659 . 10.1523/JNEUROSCI.0958-09.2009 .
  9. Foltz DR, Santiago MC, Berechid BE, Nye JS . Glycogen synthase kinase-3beta modulates notch signaling and stability . Curr. Biol. . 12 . 12 . 1006–11 . June 2002 . 12123574 . 10.1016/s0960-9822(02)00888-6. 15884556 . free . 2002CBio...12.1006F .
  10. Sade H, Krishna S, Sarin A . The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells . J. Biol. Chem. . 279 . 4 . 2937–44 . January 2004 . 14583609 . 10.1074/jbc.M309924200 . 42454311 . free.
  11. Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD . MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors . Nat. Genet. . 26 . 4 . 484–9 . December 2000 . 11101851 . 10.1038/82644 . 23335042 .
  12. Wu L, Sun T, Kobayashi K, Gao P, Griffin JD . Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors . Mol. Cell. Biol. . 22 . 21 . 7688–700 . November 2002 . 12370315 . 135662 . 10.1128/mcb.22.21.7688-7700.2002.
  13. Blokzijl A, Dahlqvist C, Reissmann E, Falk A, Moliner A, Lendahl U, Ibáñez CF . Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3 . J. Cell Biol. . 163 . 4 . 723–8 . November 2003 . 14638857 . 2173673 . 10.1083/jcb.200305112 .
  14. Guan E, Wang J, Laborda J, Norcross M, Baeuerle PA, Hoffman T . T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells . J. Exp. Med. . 183 . 5 . 2025–32 . May 1996 . 8642313 . 2192574 . 10.1084/jem.183.5.2025.
  15. Wang J, Shelly L, Miele L, Boykins R, Norcross MA, Guan E . Human Notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain . J. Immunol. . 167 . 1 . 289–95 . July 2001 . 11418662 . 10.4049/jimmunol.167.1.289. 22399328 . free .
  16. Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, Perbal B, Katsube K . The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway . J. Biol. Chem. . 277 . 33 . 29399–405 . August 2002 . 12050162 . 10.1074/jbc.M203727200 . 26465428 . free .
  17. Nam Y, Weng AP, Aster JC, Blacklow SC . Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex . J. Biol. Chem. . 278 . 23 . 21232–9 . June 2003 . 12644465 . 10.1074/jbc.M301567200 . 13637961 . free .
  18. Aster JC, Robertson ES, Hasserjian RP, Turner JR, Kieff E, Sklar J . Oncogenic forms of NOTCH1 lacking either the primary binding site for RBP-Jkappa or nuclear localization sequences retain the ability to associate with RBP-Jkappa and activate transcription . J. Biol. Chem. . 272 . 17 . 11336–43 . April 1997 . 9111040 . 10.1074/jbc.272.17.11336. 36236215 . free .
  19. Beatus P, Lundkvist J, Oberg C, Pedersen K, Lendahl U . The origin of the ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity . Mech. Dev. . 104 . 1–2 . 3–20 . June 2001 . 11404076 . 10.1016/s0925-4773(01)00373-2. 9526831 .
  20. Zhou S, Fujimuro M, Hsieh JJ, Chen L, Miyamoto A, Weinmaster G, Hayward SD . SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function . Mol. Cell. Biol. . 20 . 7 . 2400–10 . April 2000 . 10713164 . 85419 . 10.1128/mcb.20.7.2400-2410.2000.
  21. Chastagner P, Israël A, Brou C . AIP4/Itch regulates Notch receptor degradation in the absence of ligand . PLOS ONE . 3 . 7 . e2735 . 18628966 . 2444042 . 10.1371/journal.pone.0002735 . 2008PLoSO...3.2735C . 2008 . free .
  22. Yeh TS, Lin YM, Hsieh RH, Tseng MJ . Association of transcription factor YY1 with the high molecular weight Notch complex suppresses the transactivation activity of Notch . J. Biol. Chem. . 278 . 43 . 41963–9 . October 2003 . 12913000 . 10.1074/jbc.M304353200 . 23574059 . free .
  23. Lim R, Sugino T, Nolte H, Andrade J, Zimmermann B, Shi C, Doddaballapur A, Ong YT, Wilhelm K, Fasse JW, Ernst A, Kaulich M, Husnjak K, Boettger T, Guenther S, Braun T, Krüger M, Benedito R, Dikic I, Potente M . Deubiquitinase USP10 regulates Notch signaling in the endothelium. . Science . 364 . 6436 . 188–193 . April 2019 . 30975888 . 10.1126/science.aat0778 . 2019Sci...364..188L . 20.500.12105/9685 . 109940358 . free .

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