NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain

被引：47

作者：

Luo, Zhiyuan ^{[1
]}

Mu, Lili ^{[1
]}

Zheng, Yue ^{[1
]}

Shen, Wenchen ^{[1
]}

Li, Jiali ^{[1
]}

Xu, Lichao ^{[1
]}

Zhong, Bo ^{[1
]}

Liu, Ying ^{[1
]}

Zhou, Yan ^{[1
]}

机构：

[1] Wuhan Univ, Sch Med, Renmin Hosp, Med Res Inst,Coll Life Sci, Wuhan 430072, Peoples R China

来源：

JOURNAL OF MOLECULAR CELL BIOLOGY | 2020年 / 12卷 / 05期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

NUMB; Notch intracellular domain; BAP1; ubiquitination; neural progenitor cells; ASYMMETRIC CELL-DIVISION; NEURAL STEM-CELLS; ANTAGONIZES NOTCH; PROGENITOR CELLS; FAMILY PROTEINS; ACTIVATION; COMPLEX; BAP1; TRAFFICKING; SEL-10;

D O I：

10.1093/jmcb/mjz088

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The release and nuclear translocation of the intracellular domain of Notch receptor (NICD) is the prerequisite for Notch signalingmediated transcriptional activation. NICD is subjected to various posttranslational modifications including ubiquitination. Here, we surprisingly found that NUMB proteins stabilize the intracellular domain of NOTCH1 receptor (N1ICD) by regulating the ubiquitinproteasome machinery, which is independent of NUMB's role in modulating endocytosis. BAP1, a deubiquitinating enzyme (DUB), was further identified as a positive N1ICD regulator, and NUMB facilitates the association between N1ICD and BAP1 to stabilize N1ICD. Intriguingly, BAP1 stabilizes N1ICD independent of its DUB activity but relying on the BRCA1-inhibiting function. BAP1 strengthens Notch signaling and maintains stem-like properties of cortical neural progenitor cells. Thus, NUMB enhances Notch signaling by regulating the ubiquitinating activity of the BAP1-BRCA1 complex.

引用

页码：345 / 358

页数：14

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