Essential Phosphatases and a Phospho-Degron Are Critical for Regulation of SRC-3/AIB1 Coactivator Function and Turnover
作者： Chao Li , Yao-Yun Liang , Xin-Hua Feng , Sophia Y. Tsai , Ming-Jer Tsai
DOI: 10.1016/J.MOLCEL.2008.07.019
关键词:
摘要: SRC-3/AIB1 is a master growth coactivator and oncogene, phosphorylation activates it into powerful coregulator. Dephosphorylation potential regulatory mechanism for SRC-3 function, but the identity of such phosphatases remains unexplored. Herein, we report that, using functional genomic screening human Ser/Thr targeting SRC-3's known sites, PDXP, PP1, PP2A were identified to be key negative regulators transcriptional coregulatory activity in steroid receptor signalings. PDXP dephosphorylate inhibit its ligand-dependent association with estrogen receptor. PP1 stabilizes protein by blocking proteasome-dependent turnover through dephosphorylation two previously unidentified sites (Ser101 S102) required activity. These are located within degron primary determinants turnover. Moreover, regulates oncogenic cell proliferation invasion functions breast cancer cells.
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