Involvement of the molecular chaperone Ydj1 in the ubiquitin-dependent degradation of short-lived and abnormal proteins in Saccharomyces cerevisiae
Involvement of the molecular chaperone Ydj1 in the ubiquitin-dependent degradation of short-lived and abnormal proteins in Saccharomyces cerevisiae
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分子伴侣 Ydj1 参与酿酒酵母中短寿命和异常蛋白的泛素依赖性降解
DOI：
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发表时间：
1996
影响因子：
5.3
通讯作者：
Andalfred L. Goldberg
中科院分区：
文献类型：
--
作者：
Do Hee Lee;Michael Y. Sherman;Andalfred L. Goldberg
在大肠杆菌和线粒体中，分子伴侣DNAJ不仅是蛋白质折叠所必需的，而且对某些异常多肽的选择性降解也是必需的。在这里，我们证明了在酵母胞浆中，同源伴侣Ydj1也是依赖泛素降解某些异常蛋白质所必需的。温度敏感的ydj1-151突变体在短寿命细胞蛋白和含有氨基酸类似物的异常多肽的整体分解方面存在很大缺陷，特别是在38℃。相比之下，不依赖泛素的长寿命细胞蛋白的降解没有改变，也没有影响细胞生长。Ydj1的失活显著减少了某些β-半乳糖苷酶(β-GAL)融合多肽的快速、泛素依赖的分解。尽管N-末端规则底物(精氨酸-β-半乳糖和亮氨酸-β-半乳糖)和B型细胞周期蛋白Clb5-β-半乳糖的降解正常发生，但异常多肽泛素-脯氨酸-β-半乳糖(Ub-P-β-Gal)和短暂的正常蛋白Gcn4的降解受到抑制。由于Ub-P-β-Gal降解减少，温度敏感的ydj1-151突变细胞中的β-Gal活性是野生型细胞的四到五倍；因此，这种酶的折叠和组装不需要Ydj1功能。在野生型细胞中，但在ydj1-151突变细胞中，该伴侣与短暂的底物Ub-P-β-Gal有关，而与稳定的β-Gal结构无关。此外，在ydj1-151突变体中，Ub-P-β-Gal的泛素化被阻断，细胞内泛素化蛋白的总水平降低。因此，Ydj1对于依赖泛素的某些蛋白质的降解是必不可少的。这种伴侣可以促进对未折叠蛋白质的识别，或作为某些泛素连接酶的辅因子。
In Escherichia coli and mitochondria, the molecular chaperone DnaJ is required not only for protein folding but also for selective degradation of certain abnormal polypeptides. Here we demonstrate that in the yeast cytosol, the homologous chaperone Ydj1 is also required for ubiquitin-dependent degradation of certain abnormal proteins. The temperature-sensitive ydj1-151 mutant showed a large defect in the overall breakdown of short-lived cell proteins and abnormal polypeptides containing amino acid analogs, especially at 38 degrees C. By contrast, the degradation of long-lived cell proteins, which is independent of ubiquitin, was not altered nor was cell growth affected. The inactivation of Ydj1 markedly reduced the rapid, ubiquitin-dependent breakdown of certain beta-galactosidase (beta-gal) fusion polypeptides. Although degradation of N-end rule substrates (arginine-beta-gal and leucine-beta-gal) and the B-type cyclin Clb5-beta-gal occurred normally, degradation of the abnormal polypeptide ubiquitin-proline-beta-gal (Ub-P-beta-gal) and that of the short-lived normal protein Gcn4 were inhibited. As a consequence of reduced degradation of Ub-P-beta-gal, the beta-gal activity was four to five times higher in temperature-sensitive ydj1-151 mutant cells than in wild-type cells; thus, the folding and assembly of this enzyme do not require Ydj1 function. In wild-type cells, but not in ydj1-151 mutant cells, this chaperone is associated with the short-lived substrate Ub-P-beta-gal and not with stable beta-gal constructs. Furthermore, in the ydj1-151 mutant, the ubiquitination of Ub-P-beta-gal was blocked and the total level of ubiquitinated protein in the cell was reduced. Thus, Ydj1 is essential for the ubiquitin-dependent degradation of certain proteins. This chaperone may facilitate the recognition of unfolded proteins or serve as a cofactor for certain ubiquitin-ligating enzymes.
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DnaK 和 DnaJ 热休克蛋白参与大肠杆菌中的蛋白质输出。
影响因子：
10.5
作者：
Wild,J;Altman,E;Yura,T;Gross,CA
通讯作者：
Gross,CA
影响因子：
56.9
作者：
BACHMAIR, A;FINLEY, D;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
酿酒酵母中的三个蛋白水解系统。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jones,EW
通讯作者：
Jones,EW
DOI：
10.1016/s0021-9258(19)36777-8
发表时间：
1992-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. Cyr;Xiangyang Lu;M. Douglas
通讯作者：
D. Cyr;Xiangyang Lu;M. Douglas
DOI：
10.1073/pnas.88.16.7351
发表时间：
1991-08-01
影响因子：
11.1
作者：
DOHMEN, RJ;MADURA, K;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A