辅助伴侣蛋白HspBP1抑制CHIP泛素连接酶并刺激囊性纤维化跨膜传导调节因子的成熟。
The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator.
作者信息
Alberti Simon, Böhse Karsten, Arndt Verena, Schmitz Anton, Höhfeld Jörg
机构信息
Institut für Zellbiologie and Bonner Forum Biomedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53121 Bonn, Germany.
出版信息
Mol Biol Cell. 2004 Sep;15(9):4003-10. doi: 10.1091/mbc.e04-04-0293. Epub 2004 Jun 23.
Abstract
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.
摘要
CHIP泛素连接酶将分子伴侣转变为蛋白质降解因子。在信号通路调控和蛋白质质量控制过程中，CHIP与分子伴侣Hsc70和Hsp90结合，并将与分子伴侣结合的底物导向蛋白酶体进行降解。显然，这种破坏活性应受到严格控制。在此，我们鉴定出共分子伴侣HspBP1是CHIP的一种抑制剂。当与Hsc70复合时，HspBP1会减弱CHIP的泛素连接酶活性。因此，HspBP1干扰CHIP诱导的囊性纤维化跨膜传导调节因子（CFTR）未成熟形式的降解，并促进CFTR成熟。我们的数据揭示了一种决定分子伴侣折叠和降解活性的新型调控机制。
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2
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Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12337-42. doi: 10.1073/pnas.2031337100. Epub 2003 Oct 2.
3
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Nature. 2003 Sep 25;425(6956):407-10. doi: 10.1038/nature01913.
4
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5
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6
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