hZimp7, a novel PIAS-like protein, enhances androgen receptor-mediated transcription and interacts with SWI/SNF-like BAF complexes
hZimp7, a novel PIAS-like protein, enhances androgen receptor-mediated transcription and interacts with SWI/SNF-like BAF complexes
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DOI：
10.1210/me.2005-0097
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发表时间：
2005-12-01
影响因子：
--
通讯作者：
Sun, ZJ
中科院分区：
文献类型：
--
作者：
Huang, CY;Beliakoff, J;Sun, ZJ
皮亚斯（活化信号转导子和转录激活子的蛋白质抑制剂）家族的成员是酪氨酸激酶（JAK）-信号转导子和转录激活子途径的Janus家族的负调节剂。近年来，研究发现皮亚斯蛋白在多种细胞过程中与多种信号通路相互作用，并且已经证实皮亚斯和类皮亚斯蛋白与核激素受体相互作用。在这项研究中，我们已经确定了一种新的人类PIAS样蛋白，暂时命名为hZimp 7，它与hZimp 10（人类含锌指，Miz 1，PIAS样蛋白10号染色体上）具有高度的序列相似性。hZimp 7（人含锌指蛋白，Miz 1，7号染色体上的PIAS样蛋白）具有约100 kDa的分子量，并含有保守的Miz（msx相互作用锌指）结构域、核转位信号序列和C末端反式激活结构域。北方印迹分析显示hZimp 7主要在睾丸、心脏、脑、前列腺和卵巢中表达。此外，前列腺组织的免疫组织化学染色显示，内源性hZimp 7蛋白定位于前列腺上皮细胞的细胞核，并与雄激素受体（AR）共染色。进一步分析hZimp 7亚细胞定位揭示hZimp 7和AR共定位于细胞核内，并在复制灶处形成蛋白复合物。瞬时转染实验表明，hZimp 7增强AR和其他核激素受体的转录活性。相反，通过RNA干扰降低内源性hZimp 7蛋白表达降低AR介导的转录。最后，我们确定，hZimp 7物理协会与Brg 1和BAF 57，组件的ATP依赖性哺乳动物SWI/SNF样BAF染色质重塑复合物。上述数据说明了hZimp 7在通过SWI/SNF样BAF复合物调节AR和/或其他核受体介导的结构中的潜在作用。
Members of the PIAS (protein inhibitor of activated signal transducer and activator of transcription) family are negative regulators of the Janus family of tyrosine kinase (JAK)-signal transducer and activator of transcription pathway. Recently, PIAS proteins have been shown to interact with multiple signaling pathways in various cellular processes, and it has been demonstrated that PIAS and PIAS-like proteins interact with nuclear hormone receptors. In this study, we have identified a novel human PIAS-like protein, provisionally termed hZimp7, which shares a high degree of sequence similarity with hZimp10 (human zinc finger-containing, Miz1, PIAS-like protein on chromosome 10). hZimp7 (human zinc finger-containing, Miz1, PIAS-like protein on chromosome 7) possesses a molecular mass of approximately 100 kDa and contains a conserved Miz (msx-interacting zinc finger) domain, a nuclear translocation signal sequence, and a C-terminal transactivation domain. Northern blot analysis revealed that hZimp7 is predominately expressed in testis, heart, brain, prostate, and ovary. Moreover, immunohistochemical staining of prostate tissues revealed that endogenous hZimp7 protein localizes to the nuclei of prostate epithelial cells and costains with the androgen receptor (AR). Further analysis of hZimp7 subcellular localization revealed that hZimp7 and the AR co-localize within the nucleus and form a protein complex at replication foci. Transient transfection experiments showed that hZimp7 augments the transcriptional activity of the AR and other nuclear hormone receptors. In contrast, reduction of endogenous hZimp7 protein expression by RNA interference decreased AR-mediated transcription. Finally, we determined that hZimp7 physically associates with Brg1 and BAF57, components of the ATP-dependent mammalian SWI/SNF-like BAF chromatin-remodeling complexes. The above data illustrate a potential role for hZimp7 in modulation of AR and/or other nuclear receptor-mediated structure by SWI/SNF-like BAF complexes.