Intracellularly inducible, ubiquitin hydrolase-insensitive tandem ubiquitins inhibit the 26S proteasome activity and cell division

被引:12
作者
Saeki, Y
Isono, E
Oguchi, T
Shimada, M
Sone, T
Kawahara, H
Yokosawa, H
Toh-e, A [1 ]
机构
[1] Univ Tokyo, Dept Biol Sci, Grad Sch Sci, Tokyo 1130033, Japan
[2] Hokkaido Univ, Dept Biochem, Grad Sch Pharmaceut Sci, Sapporo, Hokkaido 0600821, Japan
关键词
hydrolase resistant-tandem ubiquitin; inhibitor; proteasome; proteolysis; yeast;
D O I
10.1266/ggs.79.77
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We constructed polyubiquitin derivatives that contain a tandem repeat of ubiquitins and were insensitive to ubiquitin hydrolases. They were designated tandem ubiquitin (tUb) with the number of repeats, such as tUb2. When tUbs were expressed under the control of the GAL1 promoter in the wild-type yeast strain, growth was strongly inhibited. Under these conditions, the degradation of N-end rule substrates, a UFD substrate and Gcn4 was inhibited, indicating that the tUb inhibits 26S proteasome activity. Consistent with this, tUb binds to the 26S proteasome. We showed that tUb inhibited the in vitro degradation of polyubiquitinylated Sic1 by the 26S proteasome. When tUB6 messenger RNA was injected into Xenopus embryos, cell division was inhibited, suggesting that tUb can be used as a versatile inhibitor of the 26S proteasome.
引用
收藏
页码:77 / 86
页数:10
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