Yen Hsueh-Chi S, Gordon Colin, Chang Eric C
Department of Molecular and Cellular Biology, Breast Cancer Center, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Cell. 2003 Jan 24;112(2):207-17. doi: 10.1016/s0092-8674(03)00043-6.
Yin6 is a yeast homolog of Int6, which is implicated in tumorigenesis. We show that Yin6 binds to and regulates proteasome activity. Overexpression of Yin6 strengthens proteasome function while inactivation weakens and causes the accumulation of polyubiquitinated proteins including securin/Cut2 and cyclin/Cdc13. Yin6 regulates the proteasome by preferentially interacting with Rpn5, a conserved proteasome subunit, and affecting its localization/assembly. We showed previously that Yin6 cooperates with Ras1 to mediate chromosome segregation; here, we demonstrate that Ras1 similarly regulates the proteasome via Rpn5. In yeast, human Int6 binds Rpn5 and regulates its localization. We propose that human Int6, either alone or cooperatively with Ras, influences proteasome activities via Rpn5. Inactivating Int6 can lead to accumulation of mitotic regulators affecting cell division and mitotic fidelity.
Yin6是Int6的酵母同源物，Int6与肿瘤发生有关。我们发现Yin6与蛋白酶体活性结合并对其进行调节。Yin6的过表达增强了蛋白酶体功能，而失活则削弱了蛋白酶体功能并导致包括分离酶/Cut2和细胞周期蛋白/Cdc13在内的多聚泛素化蛋白的积累。Yin6通过优先与保守的蛋白酶体亚基Rpn5相互作用并影响其定位/组装来调节蛋白酶体。我们之前表明Yin6与Ras1合作介导染色体分离；在这里，我们证明Ras1同样通过Rpn5调节蛋白酶体。在酵母中，人类Int6结合Rpn5并调节其定位。我们提出，人类Int6单独或与Ras协同作用，通过Rpn5影响蛋白酶体活性。Int6失活会导致影响细胞分裂和有丝分裂保真度的有丝分裂调节因子的积累。
