CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein
CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein
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DOI：
10.1093/embo-reports/kve246
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发表时间：
2001-12-01
期刊：
影响因子：
7.7
通讯作者：
Tanaka, K
中科院分区：
文献类型：
--
作者：
Murata, S;Minami, Y;Tanaka, K
泛素-蛋白酶体系统催化立即破坏细胞中产生的错误折叠或受损的蛋白质，但这种蛋白质分解机制如何识别细胞蛋白质的异常以选择性消除仍然难以捉摸。在这里，我们报道了带有U-box结构域的Hsc70相互作用蛋白(CHIP)的C末端是一个E3泛素连接酶，与分子伴侣Hsp90和1 Hsc70合作。在体外，只有当未折叠的底物被Hsp90或Hsc70和Hsp40捕获时，热变性萤火虫荧光素酶才能在E1和E2(Ubc4或UbcH5c)存在下被CHIP多泛素化。在缺少U-box区域的芯片中未检测到泛素化活性。被Hsp90的C-末端区域捕获的高效泛素化变性荧光素酶，该区域包含一个芯片结合位点。CHIP还显示出不依赖于目标泛素化的自身泛素化活性。我们的结果表明，CHIP可以被认为是通过与分子伴侣合作来选择性泛素化未折叠蛋白(S)的质量控制E3。
The ubiquitin-proteasome system catalyses the immediate destruction of misfolded or impaired proteins generated in cells, but how this proteolytic machinery recognizes abnormality of cellular proteins for selective elimination remains elusive. Here, we report that the C-terminus of Hsc70-interacting protein (CHIP) with a U-box domain is an E3 ubiquitin-ligase collaborating with molecular chaperones Hsp90 and 1 Hsc70. Thermally denatured firefly luciferase was multiubiquitylated by CHIP in the presence of E1 and E2 (Ubc4 or UbcH5c) in vitro, only when the unfolded substrate was captured by Hsp90 or Hsc70 and Hsp40. No ubiquitylating activity was detected in CHIP lacking the U-box region. CHIP efficiently ubiquitylated denatured luciferase trapped by the C-terminal region of Hsp90, which contains a CHIP binding site. CHIP also showed self-ubiquitylating activity independent of target ubiquitylation. Our results indicate that CHIP can be regarded as 'a quality-control E3' that selectively ubiquitylates unfolded protein(s) by collaborating with molecular chaperones.