NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain

查看全文 作　　者：Zhiyuan [1]Luo;Lili [1]Mu;Yue [1]Zheng;Wenchen [1]Shen;Jiali [1]Li;Lichao [1]Xu;Bo [1]Zhong;Ying [1]Liu;Yan [1]Zhou

机构地区：[1]College of Life Sciences,Renmin Hospital of Wuhan University,Medical Research Institute at School of Medicine,Wuhan University,Wuhan 430072,China

出　　处：《Journal of Molecular Cell Biology》索引2020年第12卷第5期,共14页

基　　金：supported by grants from the National Key R&D Program of China(2018YFA0800700);the National Natural Science Foundation of China(31671418,31970676,31970770,and 31471361);Hubei Natural Science Foundation(2018CFA016);Fundamental Research Funds for the Central Universities(2042017kf0242);Medical Science Advancement Program(Basic Medical Sciences)of Wuhan University(TFJC2018005);Wuhan University Experiment Technology Project Funding(WHU-2018-SYJS-01). 摘　　要：The release and nuclear translocation of the intracellular domain of Notch receptor(NICD)is the prerequisite for Notch signaling-mediated 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 ubiquitin–proteasome 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. 关键词：NUMB Notch INTRACELLULAR domain BAP1 UBIQUITINATION neural PROGENITOR cells

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NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain

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