title: Regulation of tumor suppressor EAF2 polyubiquitination by ELL1 and SIAH2 in prostate cancer cells.
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.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.|Department of Geriatrics, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.|Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support and Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support, Guangzhou, China.
authors.forename: Xinpei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: Junkui
authors.initials: J
authors.lastname: Ai
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: Liquan
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.|Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Pascal
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA.|Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA.|University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D000098563:Seven in Absentia Proteins
chemical_list: C472771:EAF2 protein, human; C090862:ELL protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
keywords: EAF2; ELL; SIAH2; prostate cancer; ubiquitination