Lub1 participates in ubiquitin homeostasis and stress response via maintenance of cellular ubiquitin contents in fission yeast
Lub1 participates in ubiquitin homeostasis and stress response via maintenance of cellular ubiquitin contents in fission yeast
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DOI：
10.1128/mcb.24.6.2324-2331.2004
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发表时间：
2004-03-01
影响因子：
5.3
通讯作者：
Kuno, T
中科院分区：
文献类型：
--
作者：
Ogiso, Y;Sugiura, R;Kuno, T
泛素依赖的蛋白水解在应激反应中起着关键作用。为了研究这些细胞过程的机制，我们一直在研究粟酒裂殖酵母突变体，这些突变体改变了对各种胁迫条件的敏感性。在这里，我们表明，Lub 1，在芽殖酵母中的Ufd 3 p/Zzz 4p/Doa 1 p的同源物，参与泛素含量的调节。lub 1（+）基因的破坏导致单泛素和多泛素的消耗，而mRNA水平没有变化，并对各种应激条件产生超敏反应。一致的是，编码泛素的基因的过表达抑制了与lub 1突变相关的缺陷，表明胁迫条件下的lub 1突变体的表型是由于细胞内泛素在转录后水平的短缺。此外，lub 1缺失的细胞在泛素/蛋白酶体依赖的蛋白水解中表现出异常的功能，加速了泛素的降解。此外，Cdc 48，胁迫诱导的伴侣样必需ATP酶，被发现与Lub 1相互作用，这种协会可能有助于稳定的Lub 1。我们的研究结果表明，Lub 1是负责泛素稳态在蛋白质水平上通过负调控泛素降解。
Ubiquitin-dependent proteolysis plays a pivotal role in stress responses. To investigate the mechanisms of these cellular processes, we have been studying Schizosaccharomyces pombe mutants that have altered sensitivities to various stress conditions. Here, we showed that Lub1, a homologue of Ufd3p/Zzz4p/Doa1p in budding yeast, is involved in the regulation of ubiquitin contents. Disruption of the lub1(+) gene resulted in monoubiquitin as well as multiubiquitin depletion without change in mRNA level and in hypersensitivity to various stress conditions. Consistently, overexpression of genes encoding ubiquitin suppressed the defects associated with lub1 mutation, indicating that the phenotypes of the lub1 mutants under stress conditions were due to cellular ubiquitin shortage at the posttranscriptional level. In addition, the lub1-deleted cells showed aberrant functions in ubiquitin/proteasome-dependent proteolysis, with accelerated degradation of ubiquitin. Also Cdc48, a stress-induced chaperon-like essential ATPase, was found to interact with Lub1, and this association might contribute to the stabilization of Lub1. Our results indicated that Lub1 is responsible for ubiquitin homeostasis at the protein level through a negative regulation of ubiquitin degradation.