Vinexin β interacts with the non-phosphorylated AF-1 domain of retinoid receptor γ(RARγ) and represses RARγ-mediated transcription
Vinexin β interacts with the non-phosphorylated AF-1 domain of retinoid receptor γ(RARγ) and represses RARγ-mediated transcription
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DOI：
10.1074/jbc.m501344200
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发表时间：
2005-04-29
影响因子：
4.8
通讯作者：
Rochette-Egly, C
中科院分区：
文献类型：
--
作者：
Bour, G;Plassat, JL;Rochette-Egly, C
核视黄酸受体（RAR）是配体依赖性转录因子，调节视黄酸靶基因的表达。尽管 RAR 磷酸化在 N 端结构域的重要性已明确，但受体磷酸化依赖性转录活性的潜在机制尚未阐明。在这里，我们使用酵母双杂交系统，报告分离了 vinexin beta 作为一种新的辅因子，与 RAR γ 同种型的 N 端 A/B 结构域相互作用。 Vinexin beta 是一种含有多个 SH3 基序的蛋白质，与细胞骨架相关，也存在于细胞核中。我们证明，vinexin beta 与 RAR gamma 在细胞核中共定位，并与 RAR gamma 的 AF-1 结构域的非磷酸化形式相互作用。我们还表明，AF-1 结构域磷酸化后可以阻止这种相互作用。使用稳定过表达 vinexin β 或通过 RNA 干扰敲低 vinexin 的 F9 细胞，我们证明 vinexin β 是 RAR γ 介导的转录的抑制剂。我们提出了一个模型，其中 AF-1 结构域的磷酸化通过触发 vinexin beta 的解离来控制 RAR γ 介导的转录。
Nuclear retinoic acid receptors (RARs) are ligand-dependent transcription factors that regulate the expression of retinoic acid target genes. Although the importance of RAR phosphorylation in their N-terminal domain is clearly established, the underlying mechanism for the phosphorylation-dependent transcriptional activity of the receptors had not been elucidated yet. Here, using a yeast two-hybrid system, we report the isolation of vinexin beta as a new cofactor that interacts with the N-terminal A/B domain of the RAR gamma isotype. Vinexin beta is a multiple SH3 motif-containing protein associated with the cytoskeleton and also present in the nucleus. We demonstrate that vinexin beta colocalizes with RAR gamma in the nucleus and interacts with the non-phosphorylated form of the AF-1 domain of RAR gamma. We also show that this interaction is prevented upon phosphorylation of the AF-1 domain. Using F9 cells stably overexpressing vinexin beta or vinexin knockdown by RNA interference, we demonstrate that vinexin beta is an inhibitor of RAR gamma-mediated transcription. We propose a model in which phosphorylation of the AF-1 domain controls RAR gamma-mediated transcription through triggering the dissociation of vinexin beta.