The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator
The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator
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DOI：
10.1091/mbc.e04-04-0293
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发表时间：
2004-09-01
影响因子：
3.3
通讯作者：
Höhfeld, J
中科院分区：
文献类型：
--
作者：
Alberti, S;Böhse, K;Höhfeld, J
芯片泛素连接酶将分子伴侣转化为蛋白质降解因子。ChIP与伴侣Hsc70和Hsp90结合，在信号通路的调节和蛋白质质量控制期间，将伴侣结合的客户引导到蛋白酶体进行降解。显然，这种破坏性活动应该受到谨慎的控制。在这里，我们确定辅伴侣HspBP1是一种芯片抑制因子。HspBP1与Hsc70结合可减弱CHIP的泛素连接酶活性。因此，HspBP1干扰了芯片诱导的囊性纤维化跨膜电导调节因子(CFTR)未成熟形式的降解，并刺激CFTR成熟。我们的数据揭示了一种新的调控机制，它决定了分子伴侣的折叠和降解活性。
The CHIP ubiquitin ligase turns molecular chaperones into protein degradation factors. CHIP associates with the chaperones Hsc70 and Hsp90 during the regulation of signaling pathways and during protein quality control, and directs chaperone-bound clients to the proteasome for degradation. Obviously, this destructive activity should be carefully controlled. Here, we identify the cochaperone HspBP1 as an inhibitor of CHIP. HspBP1 attenuates the ubiquitin ligase activity of CHIP when complexed with Hsc70. As a consequence, HspBP1 interferes with the CHIP-induced degradation of immature forms of the cystic fibrosis transmembrane conductance regulator (CFTR) and stimulates CFTR maturation. Our data reveal a novel regulatory mechanism that determines folding and degradation activities of molecular chaperones.