Post-translational Down-regulation of Melanoma Antigen-A11 (MAGE-A11) by Human p14-ARF Tumor Suppressor.

The Journal of Biological Chemistry
John T MingesElizabeth M Wilson

Abstract

X-linked primate-specific melanoma antigen-A11 (MAGE-A11) is a human androgen receptor (AR) coactivator and proto-oncogene expressed at low levels in normal human reproductive tract tissues and at higher levels in castration-resistant prostate cancer where it is required for androgen-dependent cell growth. In this report, we show that MAGE-A11 is targeted for degradation by human p14-ARF, a tumor suppressor expressed from an alternative reading frame of the p16 cyclin-dependent kinase inhibitor INK4a/ARF gene. MAGE-A11 degradation by the proteasome was mediated by an interaction with p14-ARF and was independent of lysine ubiquitination. A dose-dependent inverse relationship between MAGE-A11 and p14-ARF correlated with p14-ARF inhibition of the MAGE-A11-induced increase in androgen-dependent AR transcriptional activity and constitutive activity of a splice variant-like AR. Reciprocal stabilization between MAGE-A11 and AR did not protect against degradation promoted by p14-ARF. p14-ARF prevented MAGE-A11 interaction with the E2F1 oncoprotein and inhibited the MAGE-A11-induced increase in E2F1 transcriptional activity. Post-translational down-regulation of MAGE-A11 promoted by p14-ARF was independent of HDM2, the human homologue o...Continue Reading

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Citations

Oct 30, 2016·Molecular and Cellular Endocrinology·Shifeng SuElizabeth M Wilson
Mar 27, 2018·Journal of Molecular Evolution·Christopher S Willett, Elizabeth M Wilson
Mar 13, 2020·Cancer Management and Research·Shiheng JiaWei Dai
Aug 8, 2020·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Ashley ColemonSaumya Ramanathan
Sep 15, 2020·The Journal of Biological Chemistry·Rebecca R Florke GeePatrick Ryan Potts
Dec 7, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Franco Andrés PascucciMartín Monte

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