Journal
ONCOTARGET
Volume 7, Issue 20, Pages 29245-29254Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8588
Keywords
prostate cancer; EAF2; ELL; SIAH2; ubiquitination
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Funding
- NIH [R01 CA186780]
- National Natural Science Foundation of China [81130046, 2013GXNSFEA053004]
- China Scholarship Council
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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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