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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

external resources
NCBI:1268889
REACTOME:R-HSA-2644606
PUBMED:15472075
PUBMED:17646408
PUBMED:17646409

genes
ADAM10 , JAG1 , CCNC , CDK8 , CREBBP , EP300 , KAT2A , HDAC1 , HDAC2 , HES1 , RBPJ , JAG2 , MYC , NOTCH1 , PSEN2 , RPS27A , SKP1 , ADAM17 , TBL1X , UBA52 , UBB , UBC , CUL1 , HDAC3 , KAT2B , NEURL1 , NCOR1 , NCOR2 , HDAC9 , HDAC4 , MAML1 , RBX1 , HDAC6 , HDAC5 , MAMLD1 , SNW1 , NCSTN , HEY1 , HEY2 , HEYL , DLL1 , APH1A , HDAC7 , NEURL1B , DLL4 , FBXW7 , MAML3 , PSENEN , HDAC8 , MIB1 , TBL1XR1 , HDAC11 , APH1B , HDAC10 , MAML2 , MIB2 , HES5 , MIR1281 ,