BAG-1 modulates the chaperone activity of Hsp70/Hsc70
BAG-1 modulates the chaperone activity of Hsp70/Hsc70
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DOI：
10.1093/emboj/16.16.4887
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发表时间：
1997-08-15
期刊：
影响因子：
11.4
通讯作者：
Reed, JC
中科院分区：
文献类型：
--
作者：
Takayama, S;Bimston, DN;Reed, JC
70 kDa的热休克分子伴侣家族对多种细胞过程至关重要，但目前尚不清楚这些蛋白在体内是如何调节的。我们提出的证据表明，BAG-1蛋白是Hsp70和Hsc70分子伴侣的潜在调节剂，BAG-1结合到Hsp70和Hsc70的atp酶结构域，不需要它们的羧基末端肽结合结构域，并且可以与细胞裂解物中的Hsp/Hsc70共免疫沉淀。纯化的BAG-1和Hsp/Hsc70在体外有效地形成异质复合物，BAG-1抑制Hsp/Hsc70介导的未折叠蛋白底物的体外重折叠，而BAG-1突变体不能结合Hsp/Hsc70并不影响伴侣活性。在细胞裂解物中，BAG-1与已知细胞靶点之一Bcl-2的结合被发现依赖于ATP，这与Hsp/Hsc70可能参与复合物的形成一致。BAG-1的过表达也可以保护某些细胞系免受热休克诱导的细胞死亡。Hsp/Hsc70作为BAG-1的伴侣蛋白的鉴定可能解释了BAG-1与其他几种蛋白（包括raf -1、类固醇激素受体和某些酪氨酸激酶生长因子受体）之间观察到的多种相互作用。BAG-1对Hsp/Hsc70伴侣活性的抑制作用表明，BAG-1是一种新型的伴侣调节蛋白，因此表明细胞信号传导、细胞死亡和应激反应之间存在联系。
The 70 kDa heat shock family of molecular chaperones is essential to a variety of cellular processes, yet it is unclear how these proteins are regulated in vivo, We present evidence that the protein BAG-1 is a potential modulator of the molecular chaperones, Hsp70 and Hsc70, BAG-1 binds to the ATPase domain of Hsp70 and Hsc70, without requirement for their carboxyterminal peptide-binding domain, and can be coimmunoprecipitated with Hsp/Hsc70 from cell lysates, Purified BAG-1 and Hsp/Hsc70 efficiently form heteromeric complexes in vitro, BAG-1 inhibits Hsp/Hsc70-mediated in vitro refolding of an unfolded protein substrate, whereas BAG-1 mutants that fail to bind Hsp/Hsc70 do not affect chaperone activity, The binding of BAG-1 to one of its known cellular targets, Bcl-2, in cell lysates was found to be dependent on ATP, consistent with the possible involvement of Hsp/Hsc70 in complex formation, Overexpression of BAG-1 also protected certain cell lines from heat shock-induced cell death, The identification of Hsp/Hsc70 as a partner protein for BAG-1 may explain the diverse interactions observed between BAG-1 and several other proteins, including Raf-l, steroid hormone receptors and certain tyrosine kinase growth factor receptors, The inhibitory effects of BAG-1 on Hsp/Hsc70 chaperone activity suggest that BAG-1 represents a novel type of chaperone regulatory proteins and thus suggest a link between cell signaling, cell death and the stress response.