Functional regulation of novel tumor suppressor protein Sav1 by molecular chaperone

通过高通量蛋白质组学筛选，我们确定了分子伴侣（Hsp60和Hsp70）是与Sav1（哺乳动物同源萨尔瓦多）相关的新蛋白。Sav1以聚合体为靶点，通过蛋白酶体抑制剂MG132增强其对聚合体的隔离。此外，Sav1与Hsp70和CHIP （Hsp70相互作用蛋白的羧基端）共定位，已被证明介导蛋白酶体的底物泛素化和降解。此外，抗sav1免疫染色显示与Hsp60部分共定位。在这项研究中，我们证明了Hsp60是与Sav1结合的蛋白之一。Hsp60与Sav1的相互作用可能影响Hsp60介导的信号级联反应。这项研究表明，Sav1在聚合体途径中具有先前意想不到的关键作用。

Using high throughput proteomics screening, we identified the molecular chaperones (Hsp60 and Hsp70) as a novel protein associated with Sav1 (mammalian homologue of Salvador). Sav1 targets to the aggresome and its sequestration to the aggresome is enhanced by the proteasome inhibitor MG132. Furthermore, Sav1 co-localized with Hsp70 and CHIP (carboxy terminus of Hsp70-interacting protein) that has been shown to mediate substrate ubiquitination and degradation by the proteasome. In addition, anti-Sav1 immunostainings displayed partial colocalization with Hsp60. In this study, we demonstrate that Hsp60 is one of the proteins that binds to Sav1. The interaction between Hsp60 and Sav1 could influence the Hsp60-mediated signaling cascade. This study suggest that Sav1 has a previously unexpected critical role in the aggresome pathway.