A novel splice variant of the nuclear coactivator p120 functions strongly for androgen receptor: Characteristic expression in prostate disease
A novel splice variant of the nuclear coactivator p120 functions strongly for androgen receptor: Characteristic expression in prostate disease
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DOI：
10.1507/endocrj.k07e-133
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发表时间：
2008-08-01
影响因子：
2
通讯作者：
Mori, Masatomo
中科院分区：
文献类型：
--
作者：
Hosoya, Takeshi;Monden, Tsuyoshi;Mori, Masatomo
我们克隆了核辅活化子p120(α)的一个新的剪接变异体，命名为p120β，并研究了它在几种人类前列腺疾病中的功能和表达。转染实验表明，p120β对雄激素受体(AR)具有较强的共激活作用，但对其他核受体的作用较弱。GST-下拉实验表明，p120的谷氨酰胺富集区与AR的配体结合区结合。有趣的是。P120βmRNAs主要在正常前列腺癌、雄激素敏感型前列腺癌和所有雄激素敏感型前列腺癌细胞系LNCaP中表达，而在复发癌和雄激素不敏感型前列腺癌细胞百合PC3和DU145中表达较弱。此外，siRNA下调p120α基因后，PC3细胞中的辅活化油甲状腺激素受体和PPAR-γ活性消失，但不影响ARs的活性。此外，与其他核受体的竞争分析表明，tR和PPARγ不能抑制p120β诱导的刺激。这些发现表明，虽然p120α对受体和PPARγ的配体依赖刺激是必不可少的，但p120β主要是AR的共激活蛋白。
We cloned a novel splicing variant for nuclear coactivator p120(alpha), designated as p120 beta and studied its function and expression in several human prostate diseases. Transfection assays demonstrated that p120 beta 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. p120 beta mRNAs were expressed predominantly in the normal prostate, androgen-responsive prostate cancers and all androgen-sensitive prostate cancer cell line, LNCaP, but weakly in recurrent cancers and the androgen-insensitive prostate cancer cell lilies PC3 and DU145. Furthermore, knockdown of p120 alpha by siRNA abolished coactivator activity oil thyroid hormone receptors (TR) and PPAR gamma, but did not affect that of ARs in PC3 cells. In addition, competitive assay with other nuclear receptors demonstrated that TR and PPAR gamma did not inhibit p120 beta-induced stimulation. These findings Suggested that while p120 alpha was essential for ligand-dependent stimulation of TRs and PPAR gamma, p120 beta acted as a coactivating protein predominantly for AR.