Skp2-mediated degradation of p27 regulates progression into mitosis

被引：330

作者：

Nakayama, K ^{[1
]}

Nagahama, H

Minamishima, YA

Miyake, S

Ishida, N

Hatakeyama, S

Kitagawa, M

Iemura, S

Natsume, T

Nakayama, KI ^{[1
]}

机构：

[1] JST, CREST, Kawaguchi, Saitama 3320012, Japan

[2] Tohoku Univ, Sch Med, Ctr Translat & Adv Anim Res Human Dis, Div Dev Genet, Sendai, Miyagi 9808575, Japan

[3] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka, Fukuoka 8128582, Japan

[4] AIST, Biol Informat Res Ctr, Tokyo 1350064, Japan

来源：

DEVELOPMENTAL CELL | 2004年 / 6卷 / 05期

关键词：

D O I：

10.1016/S1534-5807(04)00131-5

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Although Skp2 has; been thought to mediate the degradation of p27 at the G(1)-S transition, Skp2(-/-) cells exhibit accumulation of p27 in S-G(2) phase with over-replication. We demonstrate that Skp2(-/-)p27(-/-) mice do not exhibit the overreplication phenotype, suggesting that p27 accumulation is required for its development. Hepatocytes of Skp2(-/-) mice entered the endoduplication cycle after mitogenic stimulation, whereas this phenotype was not apparent in Skp2(-/-)p27(-/-) mice. Cdc2-associated kinase activity was lower in Skp2(-/-) cells than in wild-type cells, and a reduction in Cdc2 activity was sufficient to induce overreplication. The lack of p27 degradation in G(2) phase in Skp2(-/-) cells may thus result in suppression of Cdc2 activity and consequent inhibition of entry into M phase. These data suggest that p27 proteolysis is necessary for the activation of not only Cdk2 but also Cdc2, and that Skp2 contributes to regulation of G(2)-M progression by mediating the degradation of p27.

引用

页码：661 / 672

页数：12

共 56 条

[1] SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells [J].