Skp2 regulates androgen receptor through ubiquitin-mediated degradation independent of Akt/mTOR pathways in prostate cancer

The Prostate
Bo LiZhenbang Chen

Abstract

The intervention of advanced prostate cancer (PCa) in patients has been commonly depending on androgen deprivation therapy. Despite of tremendous research efforts, however, molecular mechanisms on AR regulation remain poorly understood, particularly for castration resistant prostate cancer (CRPC). Targeting AR and associated factors is considered an effective strategy in PCa treatment. Human prostate cancer cells were used in this study. Manipulations of Skp2 expression were achieved by Skp2 shRNA/siRNA or overexpression of plasmids. Dual luciferase reporter assay was applied for AR activity assessment. Western blot, ubiquitination assay, immunoprecipitation, and immunofluorescence were applied to detect the proteins. Our results demonstrated that Skp2 directly involves the regulation of AR expression through ubiquitination-mediated degradation. Skp2 interacted with AR protein in PCa cells, and enforced expression of Skp2 resulted in a decreased level and activity of AR. By contrast, Skp2 knockdown increased the protein accumulation and activity of AR. Importantly, changes of AR contributed by Skp2 led to subsequent alterations of PSA level in PCa cells. AR ubiquitination was significantly increased upon Skp2 overexpression but...Continue Reading

References

Apr 28, 1978·Biochemical and Biophysical Research Communications·A CiehanoverA Hershko
Dec 20, 1990·The Journal of Steroid Biochemistry and Molecular Biology·J TrapmanA O Brinkmann
Mar 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·A CiechanoverA Hershko
Mar 1, 1994·DNA and Cell Biology·R A EdelsteinM R Freeman
Feb 9, 1999·Vitamins and Hormones·A K RoyB Chatterjee
Nov 13, 1999·Nature Cell Biology·A C CarranoM Pagano
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·M GstaigerW Krek
Nov 7, 2002·Cell·Derek P BrazilBrian A Hemmings
Apr 15, 2004·Endocrine Reviews·Cynthia A Heinlein, Chawnshang Chang
Jan 11, 2005·Nucleic Acids Research·Luke GaughanCraig N Robson
Mar 24, 2005·Journal of Cellular and Molecular Medicine·Gang SongShideng Bao
Aug 30, 2005·Experimental Gerontology·Marta Martinez-VicenteAna Maria Cuervo
Mar 23, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kenneth J Pienta, Deborah Bradley
Apr 6, 2006·Journal of Biosciences·Dipankar NandiDilip Chandu
May 27, 2008·Nature Reviews. Cancer·David Frescas, Michele Pagano
Jul 17, 2008·Journal of Cell Science·Hongbo WangLiang Zhu
Jan 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Anna DubrovskaVenkateshwar A Reddy
May 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Vijayabaskar LakshmikanthanYehia Daaka
Jan 19, 2010·Cell Cycle·Wei-Lei YangHui-Kuan Lin
Dec 9, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anna DubrovskaPeter G Schultz
Feb 15, 2011·Endocrine-related Cancer·Susan HaSusan K Logan
Apr 9, 2011·Trends in Cell Biology·Izumi V Hinkson, Joshua E Elias
Feb 11, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chien-Feng LiHsuan-Ying Huang
Mar 2, 2013·Molecular Endocrinology·Wenfu LuZhenbang Chen

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Citations

Mar 4, 2015·International Journal of Molecular Sciences·Zhenbang Chen, Wenfu Lu
Feb 24, 2015·Cancer Cell International·Ammad Ahmad Farooqi, Fazlul H Sarkar
May 7, 2015·Journal of Molecular Endocrinology·Kyle T HelzerElaine T Alarid
Mar 27, 2015·Current Opinion in Oncology·Jianfei QiArif Hussain
Jan 11, 2019·Cancer Research·Premkumar Vummidi GiridharSusan Kasper
Dec 5, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qi CaoXiaoping Zhang
Dec 18, 2020·The Journal of Clinical Investigation·Shidong LvZhou Wang
Nov 21, 2020·Breast Cancer Research : BCR·Shristi BhattaraiRitu Aneja

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