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Constitutive Signaling by NOTCH1 PEST Domain Mutants

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-2644606

PubChem

R-HSA-2644606

Description

As NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain mutants are expected to behave as the wild-type NOTCH1 with respect to ligand binding and proteolytic cleavage mediated activation of signaling. However, once the NICD1 fragment of NOTCH1 is released, PEST domain mutations prolong its half-life and transcriptional activity through interference with FBXW7 (FBW7)-mediated ubiquitination and degradation of NICD1 (Weng et al. 2004, Thompson et al. 2007, O'Neil et al. 2007). All NOTCH1 PEST domain mutants annotated here (NOTCH1 Q2395*, NOTCH1 Q2440*, NOTCH1 P2474Afs*4 and NOTCH1 P2514Rfs*4) either have a truncated PEST domain or lack the PEST domain completely.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 33 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O00548	Delta-like protein 1	DLL1 UNQ146/PRO172	view
O14672	Disintegrin and metalloproteinase domain-containing protein 10	ADAM10 KUZ MADM	view
O15379	Histone deacetylase 3	HDAC3	view
O60907	F-box-like/WD repeat-containing protein TBL1X	TBL1 TBL1X	view
O75376	Nuclear receptor corepressor 1	KIAA1047 NCOR1	view
P01106	Myc proto-oncogene protein	BHLHE39 MYC	view
P46531	Neurogenic locus notch homolog protein 1	NOTCH1 TAN1	view
P49336	Cyclin-dependent kinase 8	CDK8	view
P56524	Histone deacetylase 4	HDAC4 KIAA0288	view
P62979	Ubiquitin-ribosomal protein eS31 fusion protein	RPS27A UBA80 UBCEP1	view

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