Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245, USA.
J Biol Chem. 2012 Aug 3;287(32):26788-95. doi: 10.1074/jbc.M112.351825. Epub 2012 Jun 20.
Vms1 is a newly identified Cdc48-binding protein. The biological function of Vms1 remains obscure. Here, we show that both Cdc48 and Vms1, but not Cdc48 cofactors Ufd1 and Ufd2, are crucial for the degradation of Cdc13, a telomere regulator. Interestingly, both autophagy and the proteasome are involved in Cdc13 turnover. Toxicity associated with accumulation of large amounts of Cdc13 in vms1Δ or autophagy mutants underscores the significance of the proteolytic regulation of Cdc13. Because few ubiquitylated yeast proteins are known to be degraded by autophagy under non-stress conditions, the identification of Cdc13 as a target of autophagy provides a valuable tool to unravel the mechanism of autophagy-mediated selective protein degradation.
Vms1 是一种新鉴定的 Cdc48 结合蛋白。Vms1 的生物学功能尚不清楚。在这里，我们表明 Cdc48 和 Vms1（但不是 Cdc48 辅助因子 Ufd1 和 Ufd2）对于端粒调节剂 Cdc13 的降解至关重要。有趣的是，自噬和蛋白酶体都参与了 Cdc13 的周转。在 vms1Δ 或自噬突变体中，由于大量 Cdc13 的积累而导致的毒性突显了 Cdc13 蛋白水解调节的重要性。因为在非应激条件下，已知很少有泛素化的酵母蛋白通过自噬降解，所以将 Cdc13 鉴定为自噬的靶标为揭示自噬介导的选择性蛋白降解的机制提供了一个有价值的工具。
