Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast

被引：178

作者：

Osaka, F

Saeki, M

Katayama, S

Aida, N

Toh-e, A

Kominami, K

Toda, T

Suzuki, T

Chiba, T

Tanaka, K

Kato, S

机构：

[1] Sagami Chem Res Ctr, Japan Sci & Technol Corp, ERATO, Kato Cytoprot Network Project, Kanagawa 2290012, Japan

[2] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Tokyo 1130033, Japan

[3] Tokyo Metropolitan Inst Med Sci, Bunkyo Ku, Tokyo 1138613, Japan

[4] Japan Sci & Technol Corp, CREST, Bunkyo Ku, Tokyo 1138613, Japan

[5] Imperial Canc Res Fund, Lab Cell Regulat, London WC2A 3PX, England

来源：

EMBO JOURNAL | 2000年 / 19卷 / 13期

关键词：

cullin; NEDD8; Rub1; SCF; ubiquitin;

D O I：

10.1093/emboj/19.13.3475

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：

A ubiquitin-like modifier, NEDD8, is covalently attached to cullin-family proteins, but its physiological role is poorly understood. Here we report that the NEDD8-modifying pathway is essential for cell viability and function of Pcu1 (cullin-1 orthologue) in fission yeast. Pcu1 assembled on SCF ubiquitin-ligase was completely modified by NEDD8, Pcu1(K713R) defective for NEDD8 conjugation lost the ability to complement lethality due to pcu1 deletion. Forced expression of Pcu1(K713R) or depletion of NEDD8 in cells resulted in impaired cell proliferation and marked stabilization of the cyclin-dependent kinase inhibitor Rum1, which is a substrate of the SCF complex. Based on these findings, we propose that covalent modification of cullin-1 by the NEDD8 system plays an essential role in the function of SCF in fission yeast.

引用

页码：3475 / 3484

页数：10

共 62 条

[41]

MORENO S, 1991, METHOD ENZYMOL, V194, P795

[42] REGULATION OF PROGRESSION THROUGH THE G1 PHASE OF THE CELL-CYCLE BY THE RUM1(+) GENE [J].