title: Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast.
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.
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Osaka
authors.forename: M
authors.initials: M
authors.lastname: Saeki
authors.forename: S
authors.initials: S
authors.lastname: Katayama
authors.forename: N
authors.initials: N
authors.lastname: Aida
authors.forename: A
authors.initials: A
authors.lastname: Toh-E
authors.forename: K
authors.initials: K
authors.lastname: Kominami
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Chiba
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Kato
mesh_terms: D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases; D012568:Schizosaccharomyces / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D010453:Peptide Synthases