USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency

查看全文 作　　者：Xingyu [1,2]Liu;Yuying [3]Yao;Huiguo [1]Ding;Chuanchun [3]Han;Yuhan [2]Chen;Yuan [2]Zhang;Chanjuan [2]Wang;Xin [4]Zhang;Yiling [5]Zhang;Yun [1]Zhai;Ping [6]Wang;Wenyi [7]Wei;Jing [8]Zhang;Lingqiang [2,3]Zhang

机构地区：[1]Department of Hepatology and Gastroenterology,Beijing Youan Hospital,Capital Medical University,Beijing,China;[2]State Key Laboratory of Proteomics,Beijing Proteome Research Center,Beijing Institute of Radiation Medicine,Collaborative Innovation Center for Cancer Medicine,Beijing,China;[3]Institute of Cancer Stem Cell,Dalian Medical University,Dalian,China;[4]College of Life Sciences,Xiamen University,Xiamen,China;[5]Department of Orthopedics,the General Hospital of Chinese People’s Liberation Army,Beijing,China;[6]Shanghai Key Laboratory of Regulatory Biology,Institute of Biomedical Sciences and School of Life Sciences,East China Normal University,Shanghai,China;[7]Department of Pathology,Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,Massachusetts,USA;[8]Department of Microbiology and Immunology,Indiana University School of Medicine,Indianapolis,Indiana,USA

出　　处：《Signal Transduction and Targeted Therapy》索引2016年第1卷第1期,共10页

基　　金：This work was supported by Chinese National Basic Research Programs(2013CB910803);the Program of International S&T Cooperation(2014DFB30020);Chinese National Natural Science Foundation Projects(81521064);the NIH funding GM094777. 摘　　要：The homeobox transcription factor Nanog has a vital role in maintaining pluripotency and self-renewal of embryonic stem cells(ESCs).Stabilization of Nanog proteins is essential for ESCs.The ubiquitin–proteasome pathway mediated by E3 ubiquitin ligases and deubiquitylases is one of the key ways to regulate protein levels and functions.Although ubiquitylation of Nanog catalyzed by the ligase FBXW8 has been demonstrated,the deubiquitylase that maintains the protein levels of Nanog in ESCs yet to be defined.In this study,we identify the ubiquitin-specific peptidase 21(USP21)as a deubiquitylase for Nanog,but not for Oct4 or Sox2.USP21 interacts with Nanog protein in ESCs in vivo and in vitro.The C-terminal USP domain of USP21 and the C-domain of Nanog are responsible for this interaction.USP21 deubiquitylates the K48-type linkage of the ubiquitin chain of Nanog,stabilizing Nanog.USP21-mediated Nanog stabilization is enhanced in mouse ESCs and this stabilization is required to maintain the pluripotential state of the ESCs.Depletion of USP21 in mouse ESCs leads to Nanog degradation and ESC differentiation.Overall,our results demonstrate that USP21 maintains the stemness of mouse ESCs through deubiquitylating and stabilizing Nanog. 关键词：NANOG MAINTAIN STABILIZATION

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USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency

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