Interaction of U-box-type ubiquitin-protein ligases (E3s) with molecular chaperones
Interaction of U-box-type ubiquitin-protein ligases (E3s) with molecular chaperones
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DOI：
10.1111/j.1356-9597.2004.00742.x
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发表时间：
2004-06-01
期刊：
影响因子：
2.1
通讯作者：
Nakayama, KI
中科院分区：
文献类型：
--
作者：
Hatakeyama, S;Matsumoto, M;Nakayama, KI
U-box蛋白家族的成员构成了一类泛素蛋白连接酶（E3），与hect型和环指E3家族不同。两种具有代表性的哺乳动物U-box蛋白UFD2a和CHIP分别与分子伴侣蛋白VCP和Hsp90或Hsc70相互作用，并与受损蛋白的降解有关。我们现在通过对酵母双杂交系统中与这些蛋白相互作用的分子进行全面筛选，研究了哺乳动物U-box蛋白的作用。所有测试的哺乳动物U-box蛋白均发现与分子伴侣或合作伴侣相互作用，包括Hsp90、Hsp70、DnaJc7、EKN1、CRN和VCP。这些观察结果表明，U盒型E3s的功能是介导未折叠或错误折叠蛋白质的降解，并与分子伴侣作为识别这些异常蛋白质的受体。
Members of the U-box family of proteins constitute a class of ubiquitin-protein ligases (E3s) distinct from the HECT-type and RING finger-containing E3 families. Two representative mammalian U-box proteins, UFD2a and CHIP, interact with the molecular chaperones VCP and either Hsp90 or Hsc70, respectively, and are implicated in the degradation of damaged proteins. We have now investigated the roles of mammalian U-box proteins by performing a comprehensive screen for molecules that interact with these proteins in the yeast two-hybrid system. All mammalian U-box proteins tested were found to interact with molecular chaperones or cochaperones, including Hsp90, Hsp70, DnaJc7, EKN1, CRN, and VCP. These observations suggest that the function of U box-type E3s is to mediate the degradation of unfolded or misfolded proteins in conjunction with molecular chaperones as receptors that recognize such abnormal proteins.