Impaired Proteasome Function Rescues Thermosensitivity of Yeast Cells Lacking the Coatomer Subunit ε-COP*

Impaired Proteasome Function Rescues Thermosensitivity of Yeast Cells Lacking the Coatomer Subunit ε-COP*
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受损的蛋白酶体功能可恢复缺乏涂层亚基 ε-COP* 的酵母细胞的热敏感性

DOI:
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发表时间:
2000
影响因子:
4.8
通讯作者:
K. Kohno
K. Kohno
中科院分区:
生物学2区
文献类型:
--
作者:
Y. Kimata;H. Higashio;K. Kohno

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COPI 包被的转运囊泡的形成需要由七个亚基组成的胞质蛋白复合物:α-、β-、β'-、γ-、δ-、ε- 和 ζ-COP,统称为包被体。编码ε-COP亚基的酵母酿酒酵母基因被称为SEC28/ANU2。 anu2 无效突变细胞 (anu2Δ) 对温度敏感,当这些细胞转移到限制温度时,α-COP 会迅速降解。我们分离出外源抑制因子,可以挽救 anu2Δ 细胞的温度敏感生长缺陷。遗传分析显示,其中一个抑制子是等位基因 toPRE8 (PRS4),它编码 20 S 蛋白酶体亚基。在蛋白酶体抑制剂存在下,MG132,anu2Δ细胞即使在限制温度下也不会停止生长。此外,MG132 抑制 anu2Δ 细胞转向限制温度时 α-COP 水平的快速下降。然而,即使存在 MG132,这些细胞对某些蛋白质的分泌也会受到损害。总之,蛋白酶体依赖性蛋白水解作用的受损挽救了 anu2Δ 细胞的一些但不是全部的温度敏感缺陷。这些结果的讨论证明了 ε-COP 在维持 α-COP 结构完整性方面发挥着关键作用。
Formation of COPI-coated transport vesicles requires a cytosolic protein complex consisting of seven subunits: α-, β-, β′-, γ-, δ-, ε- and ζ-COP, collectively designated coatomer. The yeast Saccharomyces cerevisiaegene encoding the ε-COP subunit is known asSEC28/ANU2. anu2 null mutant cells (anu2Δ) are temperature-sensitive, and α-COP is rapidly degraded in these cells when they are shifted to the restrictive temperature. We isolated extragenic suppressors that rescue the temperature-sensitive growth defect of anu2Δ cells. Genetic analysis revealed that one of the suppressors is allelic toPRE8 (PRS4), which encodes a 20 S proteasome subunit. In the presence of a proteasome inhibitor, MG132,anu2Δ cells did not cease growth even at the restrictive temperature. Furthermore, MG132 inhibited the rapid decrease of α-COP levels in anu2Δ cells shifted to the restrictive temperature. However, secretion of certain proteins by these cells was impaired even in the presence of  MG132. In conclusion, impairment of proteasome-dependent proteolysis rescued some, but not all, temperature-sensitive defects of anu2Δ cells. These results are discussed in terms of evidence that ε-COP plays a critical role in maintaining the structural integrity of α-COP.
DOI: 10.1126/science.3018930
发表时间: 1986-10-10
期刊: SCIENCE
影响因子: 56.9
作者:
BACHMAIR, A;FINLEY, D;VARSHAVSKY, A
通讯作者: VARSHAVSKY, A