Woodruff Kelsey A, Richards Kyle A, Evans Melissa D, Scott Abigail R, Voas Brian M, Irelan Courtney Broshar, Olesen James B, Smaldino Philip J, Rubenstein Eric M
Ball State University.
MicroPubl Biol. 2021 Jun 1;2021. doi: 10.17912/micropub.biology.000403.
The heterotrimeric Asi ubiquitin ligase (encoded by , , and ) mediates protein degradation in the inner nuclear membrane in . Asi1p and Asi3p possess catalytic domains, while Asi2p functions as an adaptor for a subset of Asi substrates. We hypothesized the Asi complex is an important mediator of protein quality control, and we predicted that Asi would be required for optimal growth in conditions associated with elevated abundance of aberrant proteins. Loss of Asi1p or Asi3p, but not Asi2p, sensitized yeast to hygromycin B, which promotes translational infidelity by distorting the ribosome A site. Surprisingly, loss of quality control ubiquitin ligase Hul5p did not sensitize yeast to hygromycin B. Our results are consistent with a prominent role for an Asi subcomplex that includes Asi1p and Asi3p (but not Asi2p) in protein quality control.
异源三聚体Asi泛素连接酶（由、和编码）介导酵母内核膜中的蛋白质降解。Asi1p和Asi3p具有催化结构域，而Asi2p作为Asi底物子集的衔接蛋白发挥作用。我们推测Asi复合物是蛋白质质量控制的重要介质，并且预测在与异常蛋白质丰度升高相关的条件下，最佳生长需要Asi。Asi1p或Asi3p的缺失而非Asi2p的缺失，使酵母对潮霉素B敏感，潮霉素B通过扭曲核糖体A位点促进翻译错误。令人惊讶的是，质量控制泛素连接酶Hul5p的缺失并未使酵母对潮霉素B敏感。我们的结果与包含Asi1p和Asi3p（但不包括Asi2p）的Asi亚复合物在蛋白质质量控制中的重要作用一致。
