机构：[1]Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA[2]Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA[3]Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA[4]University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA[5]Department of Geriatrics, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China[6]Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[7]Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China[8]Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China[9]Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support and Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support, Guangzhou, China
RNA Polymerase II Elongation Factor (ELL)-associated factor 2 (EAF2) is a tumor suppressor frequently down-regulated in human prostate cancer. We previously reported that its binding partner ELL1 can enhance EAF2 protein stability and activity. Here we show that EAF2 can be polyubiquitinated and its degradation blocked by proteasome inhibitor. Co-immunoprecipitation detected EAF2 binding to SIAH2, an E3 ligase, and SIAH2 overexpression enhanced polyubiquitination of EAF2. Co-transfection of EAF2 binding partner ELL1 blocked EAF2 ubiquitination, providing a mechanism for EAF2 stabilization. Finally, EAF2K81R mutant, which exhibits reduced polyubiquitination and increased stability, was more potent than wild-type EAF2 in apoptosis induction. These findings suggest that SIAH2 is an E3 ligase for EAF2 polyubiquitination and ELL1 can enhance EAF2 level and function by blocking its polyubiquitination.
基金：
This work was supported in part by NIH grant R01 CA186780 (to ZW), National Natural Science Foundation of China Key Project 81130046 (to JZ) and 2013GXNSFEA053004 (to JZ). XY was a scholar supported by the China Scholarship Council.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类|1 区医学
小类|2 区肿瘤学3 区细胞生物学
最新[2025]版：
无
第一作者：
第一作者机构：[1]Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA[5]Department of Geriatrics, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China[8]Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China[9]Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support and Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support, Guangzhou, China
通讯作者：
通讯机构：[1]Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA[2]Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA[3]Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA[4]University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA
推荐引用方式(GB/T 7714)：
Xinpei Yu,Junkui Ai,Liquan Cai,et al.Regulation of tumor suppressor EAF2 polyubiquitination by ELL1 and SIAH2 in prostate cancer cells.[J].Oncotarget.2016,7(20):29245-54.doi:10.18632/oncotarget.8588.
APA：
Xinpei Yu,Junkui Ai,Liquan Cai,Yifeng Jing,Dan Wang...&Zhou Wang.(2016).Regulation of tumor suppressor EAF2 polyubiquitination by ELL1 and SIAH2 in prostate cancer cells..Oncotarget,7,(20)
MLA：
Xinpei Yu,et al."Regulation of tumor suppressor EAF2 polyubiquitination by ELL1 and SIAH2 in prostate cancer cells.".Oncotarget 7..20(2016):29245-54
医学