Control of metaphase-anaphase progression by proteolysis: cyclosome function regulated by the protein kinase A pathway, ubiquitination and localization.
Control of metaphase-anaphase progression by proteolysis: cyclosome function regulated by the protein kinase A pathway, ubiquitination and localization.
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通过蛋白水解控制中期-后期进展：由蛋白激酶 A 途径、泛素化和定位调节的环体功能。
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Yukinolbu Nakaseko
中科院分区：
文献类型：
--
作者：
M. Yanagida;Y. Yamashita;H. Tatebe;K. Ishii;Kazuki Kumada;Yukinolbu Nakaseko
泛素介导的蛋白质水解是细胞周期进程的基础。在裂殖酵母裂殖酵母中，有丝分裂细胞周期蛋白（Cdc 13），一个关键的细胞周期调节因子，被降解退出有丝分裂，而Cut 2必须被破坏的启动姐妹染色单体分离在后期。这些蛋白质的泛素化需要位于其N-末端的特殊破坏盒（DB）序列和称为后期促进复合物或环体的大的20 S复合物。在这里，我们表明，在中期-后期进展的细胞周期体功能是由蛋白激酶A（PKA）失活途径，泛素化的细胞周期体亚基，和细胞定位的目标基板。有证据表明，在细胞周期中的环体发挥多效性的作用：在亚基基因的突变显示一个共同的后期缺陷，但亚基特异性的表型，如在G1/S或G2/M转换，分隔和胞质分裂，应激反应和重金属敏感性，另外产生，这表明不同的亚基采取不同的部分复杂的环体功能。PKA的失活对于促进后期的环体的活化是重要的，可能通过亚基如Cut 9（Apc 6）的去磷酸化。Cut 4（Apc 1）是细胞周期中最大的亚基，在细胞周期阻滞和应激反应中参与细胞周期体的组装和功能调节。Cut 4是高度修饰的，可能是通过泛素化，当它没有组装到20 S的细胞核小体。Sds 23可能通过调节去泛素化而参与DB介导的泛素化，而Cut 8是Cdc 13和Cut 2与胞质分裂偶联的有效蛋白水解所必需的。出乎意料的是，蛋白水解的时间依赖于底物的细胞定位。Cdc 13沿着纺锤体富集首先消失，然后是核信号的衰减，而Cut 2在核中首先消失，然后是在中期后期进程中纺锤体信号的下降。
Ubiquitin-mediated proteolysis is fundamental to cell cycle progression. In the fission yeast Schizosaccharomyces pombe, a mitotic cyclin (Cdc13), a key cell cycle regulator, is degraded for exiting mitosis, while Cut2 has to be destroyed for the onset of sister chromatid separation in anaphase. Ubiquitination of these proteins requires the special destruction box (DB) sequences locating in their N-termini and the large, 20S complex called the anaphase-promoting complex or cyclosome. Here we show that cyclosome function during metaphase-anaphase progression is regulated by the protein kinase A (PKA) inactivation pathway, ubiquitination of the cyclosome subunit, and cellular localization of the target substrates. Evidence is provided that the cyclosome plays pleiotropic roles in the cell cycle: mutations in the subunit genes show a common anaphase defect, but subunit-specific phenotypes such as in G1/S or G2/M transition, septation and cytokinesis, stress response and heavy metal sensitivity, are additionally produced, suggesting that different subunits take distinct parts of complex cyclosome functions. Inactivation of PKA is important for the activation of the cyclosome for promoting anaphase, perhaps through dephosphorylation of the subunits such as Cut9 (Apc6). Cut4 (Apc1), the largest subunit, plays an essential role in the assembly and functional regulation of the cyclosome in response to cell cycle arrest and stresses. Cut4 is highly modified, probably by ubiquitination, when it is not assembled into the 20S cyclosome. Sds23 is implicated in DB-mediated ubiquitination possibly through regulating de-ubiquitination, while Cut8 is necessary for efficient proteolysis of Cdc13 and Cut2 coupled with cytokinesis. Unexpectedly, the timing of proteolysis is dependent on cellular localization of the substrate. Cdc13 enriched along the spindle disappears first, followed by decay of the nuclear signal, whereas Cut2 in the nucleus disappears first, followed by decline in the spindle signal during metaphase-anaphase progression.
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影响因子：
56.9
作者：
Hongtao Yu;Jan-Michael Peters;Randall W. King;A. M. Page;Philip Hieter;Marc W. Kirschner
通讯作者：
Hongtao Yu;Jan-Michael Peters;Randall W. King;A. M. Page;Philip Hieter;Marc W. Kirschner
影响因子：
10.5
作者：
CohenFix, O;Peters, JM;Koshland, D
通讯作者：
Koshland, D
影响因子：
3
作者：
Inoue, S
通讯作者：
Inoue, S
影响因子：
16
作者：
Fang, GW;Yu, HT;Kirschner, MW
通讯作者：
Kirschner, MW
影响因子：
10.5
作者：
Fang, GW;Yu, HT;Kirschner, MW
通讯作者：
Kirschner, MW