Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin alpha3.
Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin alpha3.
复制标题
共激活因子 RAC3 的核定位由二分 NLS 和输入蛋白 alpha3 介导。
DOI：
10.1016/j.bbrc.2006.06.163
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发表时间：
2006
影响因子：
3.1
通讯作者：
Chen,JDon
中科院分区：
文献类型：
--
作者：
Yeung,PercyLuk;Zhang,Aihua;Chen,JDon
核受体共激活因子RAC3（也称为SRC-3/ACTR/AIB1/p/CIP/ tran -1）属于p160共激活因子家族，参与多种生理过程和疾病。在这里，我们研究了RAC3如何转运到细胞核中，并表明它是通过两部分NLS和输入α3介导的。这种双部NLS位于保守的bHLH结构域中，其突变取消了核定位。NLS也足以引起EGFP的核输入，其活性需要NLS内的碱性氨基酸。RAC3与α3结合强烈，α3也依赖于碱性氨基酸。功能上，RAC3细胞质突变体失去了增强转录的能力，表明核定位对辅激活子功能至关重要。总之，这些结果揭示了p160共激活子核易位的先前未知机制以及共激活子中保守bHLH的关键功能。
The nuclear receptor coactivator RAC3 (also known as SRC-3/ACTR/AIB1/p/CIP/TRAM-1) belongs to the p160 coactivator family, which are involved in several physiological processes and diseases. Here we have investigated how RAC3 is translocated into the nucleus and show that it is mediated through a bipartite NLS and importin α3. This bipartite NLS is located within the conserved bHLH domain, and its mutation abolished nuclear localization. The NLS is also sufficient to cause nuclear import of EGFP, and the activity requires basic amino acids within the NLS. RAC3 binds strongly to importin α3, which also depends on the basic amino acids. Functionally, RAC3 cytoplasmic mutant loses its ability to enhance transcription, suggesting that nuclear localization is essential for coactivator function. Together, these results reveal a previous unknown mechanism for nuclear translocation of p160 coactivators and a critical function of the conserved bHLH within the coactivator.