NOTCH1 PEST 结构域突变体的持续信号传导

中文名称

通路描述

由于 NOTCH1 PEST 结构域位于细胞内，NOTCH1 PEST 结构域突变体预计在与配体结合和介导的蛋白水解切割激活信号传导方面与野生型 NOTCH1 行为相同。然而，一旦 NICD1 片段释放，PEST 结构域突变体通过干扰 FBXW7（FBW7）介导的 NICD1 泛素化和降解延长其半衰期和转录活性（Weng 等人 2004 年、Thompson 等人 2007 年、O'Neil 等人 2007 年）。此处列出的所有 NOTCH1 PEST 结构域突变体（NOTCH1 Q2395*, NOTCH1 Q2440*, NOTCH1 P2474Afs*4 和 NOTCH1 P2514Rfs*4）要么具有截短的 PEST 结构域，要么完全缺乏 PEST 结构域。

英文描述

Constitutive Signaling by NOTCH1 PEST Domain Mutants 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.

所含基因

57 个基因

ADAM10 ADAM17 APH1A APH1B CCNC CDK8 CREBBP CUL1 DLL1 DLL4 EP300 HDAC1 HDAC10 HDAC11 HDAC2 HDAC3 HDAC4 HDAC5 HDAC6 HDAC7 HDAC8 HDAC9 HES1 HES5 HEY1 HEY2 HEYL JAG1 JAG2 KAT2A KAT2B MAML1 MAML2 MAML3 MAMLD1 MIB1 MIB2 MYC NCOR1 NCOR2 NCSTN NEURL NEURL1B NOTCH1 PSEN1 PSEN2 PSENEN RBPJ RBX1 RPS27A SKP1 SNW1 TBL1X TBL1XR1 UBA52 UBB UBC