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PMID: 10880460 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 19 ·No. 13 ·2000-07-03 ·Pages 3475-84

Osaka F, Saeki M, Katayama S, Aida N, Toh-E A, Kominami K, Toda T, Suzuki T, Chiba T, Tanaka K, Kato S

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.

MeSH Terms
Amino Acid Sequence Molecular Sequence Data Peptide Synthases/metabolism SKP Cullin F-Box Protein Ligases Schizosaccharomyces/enzymology Sequence Homology, Amino Acid Ubiquitins/chemistry,metabolism
Chemicals
Ubiquitins SKP Cullin F-Box Protein Ligases Peptide Synthases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Osaka F
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.
Saeki M
Katayama S
Aida N
Toh-E A
Kominami K
Toda T
Suzuki T
Chiba T
Tanaka K
Kato S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.13.3475
Published
2000-07-03
Pages
3475-84
Language
English
Region
England
NLM ID
8208664
PMCID
PMC313942
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.13.3475 PMC Full Text View journal details
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