Mutant membrane protein of the budding yeast spindle pole body is targeted to the endoplasmic reticulum degradation pathway.
Mutant membrane protein of the budding yeast spindle pole body is targeted to the endoplasmic reticulum degradation pathway.
复制标题
芽殖酵母纺锤体极体的突变膜蛋白靶向内质网降解途径。
DOI：
10.1093/genetics/162.2.567
复制
发表时间：
2002
期刊：
影响因子：
3.3
通讯作者：
Winey,Mark
中科院分区：
文献类型：
--
作者：
McBratney,Susan;Winey,Mark
酵母MPS2或NDC1基因的突变会导致相同的纺锤体极体(SPB)复制缺陷：新形成的SPB被错误地插入核膜(NE)，阻止细胞形成两极有丝分裂纺锤体。我们先前已经证明MPS2和NDC1都编码定位于SPB的完整的膜蛋白。在这里，我们证明了CUE1是MPS2和NDC1突变的不寻常的剂量抑制因子，以前已知它在偶联蛋白结合到ER降解中起作用。Cue1p已被证明可以将可溶性泛素结合酶Ubc7p招募到ER膜的细胞质表面，在那里它可以泛化其底物，并使其被蛋白酶体降解。Mp2-1和ndc1-1也被UBC7或其伙伴UBC6的中断抑制。与野生型相比，突变的Mps2-1p蛋白水平显著降低，而CUE1的缺失使Mps2-1p的水平恢复到接近野生型的水平。我们的数据表明，Mps2p可能是内质网质量控制途径降解的靶点。
Mutation of either the yeastMPS2or theNDC1gene leads to identical spindle pole body (SPB) duplication defects: The newly formed SPB is improperly inserted into the nuclear envelope (NE), preventing the cell from forming a bipolar mitotic spindle. We have previously shown that bothMPS2andNDC1encode integral membrane proteins localized at the SPB. Here we show thatCUE1, previously known to have a role incouplingubiquitin conjugation toER degradation, is an unusual dosage suppressor of mutations inMPS2andNDC1. Cue1p has been shown to recruit the soluble ubiquitin-conjugating enzyme, Ubc7p, to the cytoplasmic face of the ER membrane where it can ubiquitinate its substrates and target them for degradation by the proteasome. Bothmps2-1andndc1-1are also suppressed by disruption ofUBC7or its partner,UBC6. The Mps2-1p mutant protein level is markedly reduced compared to wild-type Mps2p, and deletion ofCUE1restores the level of Mps2-1p to nearly wild-type levels. Our data indicate that Mps2p may be targeted for degradation by the ER quality control pathway.