ATP水解对于Bag-1M介导的糖皮质激素受体对DNA结合的抑制作用至关重要。
ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the glucocorticoid receptor.
作者信息
Hong Wei, Chen Linfeng, Liu Yunde, Gao Weizhen
机构信息
Department of Laboratory Medicine, Tianjin Medical University, 300203 Tianjin, China.
出版信息
Biochem Biophys Res Commun. 2009 Dec 4;390(1):77-81. doi: 10.1016/j.bbrc.2009.09.069. Epub 2009 Sep 22.
The 70-kDa heat shock protein (Hsp70) is involved in providing the appropriate conformation of various nuclear hormone receptors, including the glucocorticoid receptor (GR). The Bcl-2 associated athanogene 1M (Bag-1M) is known to downregulate the DNA binding by the GR. Also, Bag-1M interacts with the ATPase domain of Hsp70 to modulate the release of the substrate from Hsp70. In this study, we demonstrate that ATP hydrolysis enhances Bag-1M-mediated inhibition of the DNA binding by the GR. However, the inhibitory effect of Bag-1M was abolished when the intracellular ATP was depleted. In addition, a Bag-1M mutant lacking the interaction with Hsp70 did not influence the GR to bind DNA, suggesting the interaction of Bag-1M with Hsp70 in needed for its negative effect. These results indicate that ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the GR and Hsp70 is a mediator for this process.
70千道尔顿热休克蛋白（Hsp70）参与为包括糖皮质激素受体（GR）在内的各种核激素受体提供合适的构象。已知Bcl-2相关抗凋亡基因1M（Bag-1M）可下调GR的DNA结合。此外，Bag-1M与Hsp70的ATP酶结构域相互作用，以调节底物从Hsp70的释放。在本研究中，我们证明ATP水解增强了Bag-1M介导的对GR与DNA结合的抑制作用。然而，当细胞内ATP耗尽时，Bag-1M的抑制作用被消除。此外，缺乏与Hsp70相互作用的Bag-1M突变体不影响GR与DNA的结合，这表明Bag-1M与Hsp70的相互作用是其产生负效应所必需的。这些结果表明，ATP水解对于Bag-1M介导的对GR与DNA结合的抑制作用至关重要，并且Hsp70是该过程的介质。
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