CREB-binding protein in androgen receptor-mediated signaling.

CREB-binding protein (CBP) is a transcriptional coregulator that interacts with different DNA binding proteins and components of the general transcription machinery. CBP enhanced androgen receptor (AR)-dependent transcription under transient transfection conditions in CV-1 cells. The ligand binding domain (LBD) and residues 38-296 of the N-terminal region of AR are not ...
required because the activity of a receptor mutant devoid of these domains was augmented by coexpressed CBP. There is physical interaction between AR and CBP in vivo, as judged by coimmunoprecipitation experiments from cell extracts. Consistent with the role of CBP as a coactivator for AR, the 12S E1A adenoviral protein that inactivates CBP function strongly inhibited AR-dependent transactivation. Exogenous CBP was also capable of overcoming the inhibitory effect of AR on AP-1 activity and diminished the mutual transcriptional repression between AR and NF-kappaB (RelA). Collectively, these data imply that transcriptional interference between AR and AP-1 or NF-kappaB is mediated, at least in part, through competition for intracellular CBP and that this coactivator serves as an integrator between androgen-mediated and other signaling pathways.
Mesh Terms:
Animals, Binding Sites, COS Cells, CREB-Binding Protein, Cell Line, Humans, Kinetics, Nuclear Proteins, Protein Engineering, Rats, Receptors, Androgen, Receptors, Glucocorticoid, Sequence Deletion, Signal Transduction, Trans-Activators, Transcription Factor AP-1, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 03, 1998
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