Nucleolus-localized Def-CAPN3 protein degradation pathway and its role in cell cycle control and ribosome biogenesis  

作　　者：Shuyi Zhao Delai Huang Jinrong Peng 

机构地区：[1]College of Animal Sciences,Zhejiang University,Hangzhou,Zhejiang 310058,China [2]Department of Biology,University of Virginia,Charlottesville,VA 22904,United States

出　　处：《Journal of Genetics and Genomics》2021年第11期955-960,共6页遗传学报（英文版）

基　　金：the National Key R&D Program of China and the Natural Science Foundation of China in the order of 2018YFA0800502,2017YFA0504501,31330050.

摘　　要：The nucleolus,as the‘nucleus of the nucleus’,is a prominent subcellular organelle in a eukaryocyte.The nucleolus serves as the centre for ribosome biogenesis,as well as an important site for cell-cycle regulation,cellular senescence,and stress response.The protein composition of the nucleolus changes dynamically through protein turnover to meet the needs of cellular activities or stress responses.Recent studies have identified a nucleolus-localized protein degradation pathway in zebrafish and humans,namely the Def-CAPN3 pathway,which is essential to ribosome production and cell-cycle progression,by controlling the turnover of multiple substrates(e.g.,ribosomal small-subunit[SSU]processome component Mpp10,transcription factor p53,check-point proteins Chk1 and Wee1).This pathway relies on the Ca2þ-dependent cysteine proteinase CAPN3 and is independent of the ubiquitin-mediated proteasome pathway.CAPN3 is recruited by nucleolar protein Def from cytoplasm to nucleolus,where it proteolyzes its substrates which harbor a CAPN3 recognition-motif.Def depletion leads to the exclusion of CAPN3 and accumulation of p53,Wee1,Chk1,and Mpp10 in the nucleolus that result in cell-cycle arrest and rRNA processing abnormality.Here,we summarize the discovery of the Def-CAPN3 pathway and propose its biological role in cell-cycle control and ribosome biogenesis.

关 键 词：NUCLEOLUS Protein degradation Def CAPN3 P53 CHK1 Wee1 Mpp10 Sas10 

分 类 号：Q253[生物学—细胞生物学]