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首页> 外文期刊>Molecular and Cellular Biology >Adenovirus E1A functions as a cofactor for retinoic acid receptor beta (RAR beta) through direct interaction with RAR beta.
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Adenovirus E1A functions as a cofactor for retinoic acid receptor beta (RAR beta) through direct interaction with RAR beta.

机译：腺病毒E1A通过与RAR beta的直接相互作用充当视黄酸受体beta（RAR beta）的辅助因子。

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Transcription regulation by DNA-bound activators is thought to be mediated by a direct interaction between these proteins and TATA-binding protein (TBP), TFIIB, or TBP-associated factors, although occasionally cofactors or adapters are required. For ligand-induced activation by the retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer, the RAR beta 2 promoter is dependent on the presence of E1A or E1A-like activity, since this promoter is activated by retinoic acid only in cells expressing such proteins. The mechanism underlying this E1A requirement is largely unknown. We now show that direct interaction between RAR and E1A is a requirement for retinoic acid-induced RAR beta 2 activation. The activity of the hormone-dependent activation function 2 (AF-2) of RAR beta is upregulated by E1A, and an interaction between this region and E1A was observed, but not with AF-1 or AF-2 of RXR alpha. This interaction is dependent on conserved region III (CRIII), the 13S mRNA-specific region of E1A. Deletion analysis within this region indicated that the complete CRIII is needed for activation. The putative zinc finger region is crucial, probably as a consequence of interaction with TBP. Furthermore, the region surrounding amino acid 178, partially overlapping with the TBP binding region, is involved in both binding to and activation by AF-2. We propose that E1A functions as a cofactor by interacting with both TBP and RAR, thereby stabilizing the preinitiation complex.
机译：尽管有时需要辅因子或衔接子，但DNA结合激活剂的转录调控被认为是由这些蛋白与TATA结合蛋白（TBP），TFILB或TBP相关因子之间的直接相互作用介导的。对于视黄酸受体-类视黄醇X受体（RAR-RXR）异二聚体引起的配体诱导的激活，RAR beta 2启动子取决于E1A或类似E1A活性的存在，因为该启动子仅在细胞中被视黄酸激活表达这种蛋白质。此E1A要求的基础机制在很大程度上未知。现在，我们显示RAR与E1A之间的直接相互作用是视黄酸诱导RAR beta 2激活的必要条件。 RAR beta的激素依赖性激活功能2（AF-2）的活性由E1A上调，并且观察到该区域与E1A之间有相互作用，但没有与RXR alpha的AF-1或AF-2相互作用。这种相互作用取决于保守区III（CRIII），即E1A的13S mRNA特异性区域。在该区域内的缺失分析表明完整的CRIII是激活所必需的。可能的锌指区至关重要，可能是与TBP相互作用的结果。此外，氨基酸178周围的与TBP结合区域部分重叠的区域参与与AF-2的结合和被AF-2激活。我们建议E1A通过与TBP和RAR相互作用来充当辅因子，从而稳定预启动复合体。

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