Oncotarget

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This article has been corrected. Correction in: Oncotarget. 2019; 10:7187-7188.

Regulation of tumor suppressor EAF2 polyubiquitination by ELL1 and SIAH2 in prostate cancer cells

Xinpei Yu, Junkui Ai, Liquan Cai, Yifeng Jing, Dan Wang, Jun Dong, Laura E. Pascal, Jian Zhang, Rongcheng Luo and Zhou Wang _

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Oncotarget. 2016; 7:29245-29254. https://doi.org/10.18632/oncotarget.8588

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Abstract

Xinpei Yu1,5,8,9, Junkui Ai1, Liquan Cai1, Yifeng Jing1,6, Dan Wang1, Jun Dong1, Laura E. Pascal1, Jian Zhang7, Rongcheng Luo8, Zhou Wang1,2,3,4

1Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA

2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA

3Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA

4University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA

5Department of Geriatrics, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China

6Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

7Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China

8Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China

9Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support and Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support, Guangzhou, China

Correspondence to:

Zhou Wang, email: wangz2@upmc.edu

Rongcheng Luo, email: rongchengluo72@126.com

Keywords: prostate cancer, EAF2, ELL, SIAH2, ubiquitination

Received: October 06, 2015     Accepted: March 16, 2016     Published: April 05, 2016

ABSTRACT

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.


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