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Title: Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor
Authors: Zhou, X.E.
Suino-Powell, K.M.
Li, J. 
He, Y.
MacKeigan, J.P.
Melcher, K.
Yong, E.-L. 
Xu, H.E.
Issue Date: 19-Mar-2010
Citation: Zhou, X.E., Suino-Powell, K.M., Li, J., He, Y., MacKeigan, J.P., Melcher, K., Yong, E.-L., Xu, H.E. (2010-03-19). Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. Journal of Biological Chemistry 285 (12) : 9161-9171. ScholarBank@NUS Repository.
Abstract: Transcription activation by androgen receptor (AR), which depends on recruitment of coactivators, is required for the initiation and progression of prostate cancer, yet the mechanisms of how hormone-activated AR interacts with coactivators remain unclear. This is because AR, unlike any other nuclear receptor, prefers its own N-terminal FXXLF motif to the canonical LXXLL motifs of coactivators. Through biochemical and crystallographic studies, we identify that steroid receptor coactivator-3 (SRC3) (also named as amplified in breast cancer-1 or AIB1) interacts strongly with AR via synergistic binding of its first and third LXXLL motifs. Mutagenesis and functional studies confirm that SRC3 is a preferred coactivator for hormone-activated AR. Importantly, AR mutations found in prostate cancer patients correlate with their binding potency to SRC3, corroborating with the emerging role of SRC3 as a prostate cancer oncogene. These results provide a molecular mechanism for the selective utilization of SRC3 by hormone-activated AR, and they link the functional relationship between AR and SRC3 to the development and growth of prostate cancer. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M109.085779
Appears in Collections:Staff Publications

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