共价修饰因子NEDD8对于裂殖酵母中的SCF泛素连接酶至关重要。
Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast.
作者信息
Osaka F, Saeki M, Katayama S, Aida N, Toh-E A, Kominami K, Toda T, Suzuki T, Chiba T, Tanaka K, Kato S
机构信息
Kato Cytoprotein Network Project, ERATO, Japan Science and Technology Corporation (JST), c/o Sagami Chemical Research Center, Nishi-Ohnuma 4-4-1, Sagamihara, Kanagawa 229-0012, Department of Biological Sciences, Graduate School of Scienc.
出版信息
EMBO J. 2000 Jul 3;19(13):3475-84. doi: 10.1093/emboj/19.13.3475.
Abstract
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.
摘要
一种类泛素修饰因子NEDD8可共价连接到cullin家族蛋白上，但其生理作用却知之甚少。在此我们报道，NEDD8修饰途径对于裂殖酵母中细胞活力及Pcu1（cullin-1直系同源物）的功能至关重要。组装在SCF泛素连接酶上的Pcu1被NEDD8完全修饰。因NEDD8缀合缺陷的Pcu1(K713R)丧失了因pcu1缺失而导致的致死性互补能力。在细胞中强制表达Pcu1(K713R)或耗尽NEDD8会导致细胞增殖受损以及细胞周期蛋白依赖性激酶抑制剂Rum1显著稳定，Rum1是SCF复合物的一个底物。基于这些发现，我们提出NEDD8系统对cullin-1的共价修饰在裂殖酵母的SCF功能中起着至关重要的作用。
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