A Novel Splice Variant of the Nuclear Coactivator p120 Functions Strongly for Androgen Receptor: Characteristic Expression in Prostate Disease

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We cloned a novel splicing variant for nuclear coactivator p120(α), designated as p120β and studied its function and expression in several human prostate diseases. Transfection assays demonstrated that p120β functions as a strong coactivator for androgen receptor (AR), but weakly for other nuclear receptors. GST-pull down assay showed that a glutamine-rich region of the p120 bound to the ligand-binding domain of AR. Interestingly, p120β mRNAs were expressed predominantly in the normal prostate, androgen-responsive prostate cancers and an androgen-sensitive prostate cancer cell line, LNCaP, but weakly in recurrent cancers and the androgen-insensitive prostate cancer cell lines PC3 and DU145. Furthermore, knockdown of p120α by siRNA abolished coactivator activity on thyroid hormone receptors (TR) and PPARγ, but did not affect that of ARs in PC3 cells. In addition, competitive assay with other nuclear receptors demonstrated that TR and PPARγ did not inhibit p120β-induced stimulation. These findings suggested that while p120α was essential for ligand-dependent stimulation of TRs and PPARγ, p120β acted as a coactivating protein predominantly for AR.
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