Rosser Meredith F N, Washburn Erin, Muchowski Paul J, Patterson Cam, Cyr Douglas M
Department of Cell and Developmental Biology, University of North Carolina Chapel Hill School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
J Biol Chem. 2007 Aug 3;282(31):22267-77. doi: 10.1074/jbc.M700513200. Epub 2007 Jun 1.
The carboxyl terminus of the Hsc70-interacting protein (CHIP) is an Hsp70 co-chaperone as well as an E3 ubiquitin ligase that protects cells from proteotoxic stress. The abilities of CHIP to interact with Hsp70 and function as a ubiquitin ligase place CHIP at a pivotal position in the protein quality control system, where its entrance into Hsp70-substrate complexes partitions nonnative proteins toward degradation. However, the manner by which Hsp70 substrates are selected for ubiquitination by CHIP is not well understood. We discovered that CHIP possesses an intrinsic chaperone activity that enables it to selectively recognize and bind nonnative proteins. Interestingly, the chaperone function of CHIP is temperature-sensitive and is dramatically enhanced by heat stress. The ability of CHIP to recognize nonnative protein structure may aid in selection of slow folding or misfolded polypeptides for ubiquitination.
热休克蛋白70相互作用蛋白（CHIP）的羧基末端是一种Hsp70共伴侣蛋白，也是一种E3泛素连接酶，可保护细胞免受蛋白毒性应激。CHIP与Hsp70相互作用并作为泛素连接酶发挥作用的能力，使其在蛋白质质量控制系统中处于关键位置，在该系统中，它进入Hsp70-底物复合物会将非天然蛋白质导向降解。然而，CHIP选择Hsp70底物进行泛素化的方式尚不清楚。我们发现CHIP具有内在的伴侣活性，使其能够选择性地识别并结合非天然蛋白质。有趣的是，CHIP的伴侣功能对温度敏感，热应激可显著增强该功能。CHIP识别非天然蛋白质结构的能力可能有助于选择缓慢折叠或错误折叠的多肽进行泛素化。
