Epidermal-growth-factor-dependent phosphorylation and ubiquitinylation of MAGE-11 regulates its interaction with the androgen receptor.

Molecular and Cellular Biology
Suxia Bai, Elizabeth M Wilson

Abstract

The androgen receptor (AR) is a ligand-activated transcription factor that interacts with coregulatory proteins during androgen-dependent gene regulation. Melanoma antigen gene protein 11 (MAGE-11) is an AR coregulator that specifically binds the AR NH(2)-terminal FXXLF motif and modulates the AR NH(2)- and carboxyl-terminal N/C interaction to increase AR transcriptional activity. Here we demonstrate that epidermal growth factor (EGF) signaling increases androgen-dependent AR transcriptional activity through the posttranslational modification of MAGE-11. EGF in the presence of dihydrotestosterone stabilizes the AR-MAGE complex through the site-specific phosphorylation of MAGE-11 at Thr-360 and ubiquitinylation at Lys-240 and Lys-245. The time-dependent EGF-induced increase in AR transcriptional activity by MAGE-11 is mediated through AR activation functions 1 and 2 in association with the increased turnover of AR and MAGE-11. The results reveal a dynamic mechanism whereby growth factor signaling increases AR transcriptional activity through the covalent modification of an AR-specific coregulatory protein. Sequence conservation of the MAGE-11 phosphorylation and ubiquitinylation sites throughout the MAGE gene family suggests com...Continue Reading

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Citations

Dec 15, 2010·Biochemistry·Yaroslava A Bulynko, Bert W O'Malley
May 8, 2010·The Journal of Biological Chemistry·Emily B AskewElizabeth M Wilson
Mar 2, 2011·The Journal of Biological Chemistry·Yu ZengPrakash Kulkarni
Nov 23, 2012·The Journal of Biological Chemistry·John T MingesElizabeth M Wilson
Jul 27, 2011·Therapeutic Advances in Urology·Elizabeth M Wilson
Dec 18, 2012·Reproduction : the Official Journal of the Society for the Study of Fertility·Shun ZhangWei Li
Jun 6, 2012·Cancer Letters·María Fátima LadelfaMartín Monte
May 3, 2011·Biochimica Et Biophysica Acta·Jin WangSaadi Khochbin
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Sep 30, 2015·Molecular and Cellular Endocrinology·Mario MitkovJohn Copland
Sep 22, 2011·Vaccine·Meixiang SangBaoen Shan
Jun 15, 2011·Molecular and Cellular Endocrinology·Emily B AskewElizabeth M Wilson
Oct 30, 2016·Molecular and Cellular Endocrinology·Shifeng SuElizabeth M Wilson
Mar 17, 2017·Journal of Molecular Biology·Anna K Lee, Patrick Ryan Potts
Sep 11, 2018·Journal of Cancer Research and Therapeutics·Soodabeh Abbasi SaniMohammad Reza Abbaszadegan
Jul 16, 2013·The Journal of Biological Chemistry·Shifeng SuElizabeth M Wilson
May 26, 2017·PloS One·Julieta E LaisecaMartin Monte
Mar 27, 2018·Journal of Molecular Evolution·Christopher S Willett, Elizabeth M Wilson
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Aug 15, 2012·The Journal of Biological Chemistry·Shifeng SuElizabeth M Wilson
Sep 4, 2015·The Journal of Biological Chemistry·John T MingesElizabeth M Wilson
Sep 15, 2020·The Journal of Biological Chemistry·Rebecca R Florke GeePatrick Ryan Potts
Nov 5, 2021·Oncology Letters·Sanyan LiXianrong Zhou

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