ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the glucocorticoid receptor.
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.
Hong
Wei
W
Department of Laboratory Medicine, Tianjin Medical University, 300203 Tianjin, China. hongwei@tijmu.edu.cn
Chen
Linfeng
L
Liu
Yunde
Y
Gao
Weizhen
W
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D004247:DNA