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NOTCH1

9q34.3 HGNC:7881 MIM.190198

Wednesday 11 June 2003

Notch signaling

The Notch receptor is pre-cleaved in the Golgi and is targeted subsequently to the plasma membrane where it interacts with ligands located on neighbouring cells.

Receptor–ligand interaction results in a conformational change in the receptor, thus enabling additional cleavages by TACE and the γ-secretase complex.

This proteolytic activity enables the Notch intracellular domain (NICD) to translocate to the nucleus where it activates the transcription of target genes (e.g. the Hes and Hey family of transcriptional repressors).

Monoubiquitylation (Ub) of the ligand by mindbomb (MIB) induces endocytosis of the ligand and the Notch extracellular domain (NECD) into the ligand cells where additional signalling might be initiated.

Overall, when activated, Notch signalling enables neighbouring cells to acquire distinct phenotypes, through a process named lateral inhibition.

Pathology

- NOTCH1 germline mutations in bicuspid aortic valve (#16729972#)

- NOTCH1 is aberrantly activated in more than 50% of patients with acute lymphoblastic T-cell leukaemia (T-ALL).

- A subset of T-cell acute lymphoblastic leukemias is associated with a recurrent t(7;9)(q34;q34) translocation involving human NOTCH1.

See also

- NOTCHs

References

- Clinical and biologic characterization of T-cell Neoplasias with rearrangements of chromosome 7 band q34. Smith S, Morgan R, Gemmell R , Amylon M, Link M, Linker C, Hecht B Warnke R, Hecht F. Blood 1988 ; 71(2): 395-402. PMID #2962650#

- TAN-1 the human homolog of the Drosophilia notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, SKLAR J. Cell 1991; 66(4) : 649-661. PMID #1831692#

- T cell leukemia-associated human Notch homologue has I Kappa B-like activity and physically interacts with nuclear-factor-kappa B proteins in T cells.Guan E, Wang J, Laborda J, Norcross M, Baeuerle PA, Hoffman T.
J Exp Med 1996 ; 183(5) : 2025-2032. PMID #8642313#

- Essential roles for ankyrin repeats as transactivation domains in induction of T cell leukemia by Notch1. Aster JC, Xu l, Karnell FG, Patriub V, Pui JC, Pear WS. Molecular and Cellular Biology 2000; 20(20) : 7505-7515. PMID #11003647#

- Neoplastic transformation by Notch requires nuclear localization. Jeffries S, Capabianco AJ. Mol Cell Biol 2000; 20(11) : 3928-3941. PMID #10805736#

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