0 references

BAUS Section of Academic Urology Abstracts

British journal of surgery2014Vol. 101(Supplement_4), pp. 56–68

UL Burska, Victoria Harle, Kelly Coffey, Steven Darby, H. E. Ramsey, Luke Gaughan, Craig Robson, Mohammad Asim, Charles Massie, Heather Zecchini, H Mohammad, Ajoeb Baridi, Nuno Gomes, Vincent Zecchini, Basetti Madhu, A. Quershi, David E. Neal, Christina Sakellariou, Oussama Elhage, Osamu Ukimura, Inderbir S. Gill, Richard Smith, Christine Galustian, Prokar Dasgupta, C.E. Cox, Matthew Jefferies, Howard Kynaston, Angus Clarke, J. Dyer, John Dormer, Rakesh Heer, Eugene Tulchinsky, J Mellon, O Kitchen, Kim E. Haworth, Richard T. Bryan, Lyndon Gommersall, Christopher J. Luscombe, Anthony A. Fryer, William E. Farrell, Ali Tasleem, Anisur Rahman, Lami Yeo, R Dearing, Robert E. Lewis, Michel Alexandre Yazbek, J Clark, Rachel Hurst, Robert Mills, Mark Rochester, Frank McCarthy, Daniel Brewer, Dylan R. Edwards, Chris Parker, Colin S. Cooper, K. S. Patel, T Forshew, Greg Shaw, Francesco Marass, Muhammed Murtaza, Anne Y. Warren, B. W. Haynes, M. Corcoran, Nitzan Rosenfeld, N Rosenfeld, R Mitchell, P Saunders, R Sharpe, C Kelnar, W Wallace, R Huddart, A Norman, C Moynihan, A Horwich, C Parker, E Nicholls, D Dearnaley, A Pacey, E Goosens, H Tournaye

Abstract

The androgen receptor (AR) is a transcription factor involved in prostate cell growth and regulated by ubiquitination. Deregulation of AR signalling leads to the development of prostate cancer (PCa) with AR being the main therapeutic target in PCa. In a recent siRNA screen of deubiquitinating enzymes we identified ubiquitin-specific protease 12 (Usp12) to regulate ARmediated transcription. We report that Usp12 not only deubiquitinates AR resulting in increased AR protein levels but Usp12 itself is also increased in PCa patient samples compared to normal controls. Results: We identified Usp12 as an AR co-regulator showing decreased transcription of receptor-regulated genes upon Usp12 depletion. We now report that Usp12 silencing results in cell cycle arrest, decreased proliferation and increased apoptosis in PCa cells supporting co-stimulatory role of Usp12 on AR. Importantly, overexpression of Usp12 increased AR protein stability and transcriptional activity. Following this discovery we evaluated the levels of Usp12 in clinical samples and observed that Usp12 protein was increased in PCa patients compared to benign controls, additionally elevated nuclear Usp12 protein was observed in PCa patients when compared to controls.

Abstract

Related Papers