A new NEDD8-ligating system for cullin-4A.
NEDD8 is a ubiquitin (Ub)-like protein. Here we report a novel ubiquitinylation-related pathway for modification by NEDD8. NEDD8 was activated by an E1 (Ub-activating enzyme)-like complex, consisting of APP-BP1 and hUba3 with high respective homologies to the amino- and carboxy-terminal regions of E1 and then linked to hUbc12 (a human homolog of yeast Ub-conjugating enzyme Ubc12p). The major target protein modified by NEDD8 was found to be Hs-cullin-4A (Cul-4A), a member of the family of human cullin/Cdc53 proteins functioning as an essential component of a multifunctional Ub-protein ligase E3 complex that has a critical role in Ub-mediated proteolysis.
Kato Cytoprotein Network Project, ERATO, Japan Science and Technology Corporation (JST), Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan.
F
F
Osaka
H
H
Kawasaki
N
N
Aida
M
M
Saeki
T
T
Chiba
S
S
Kawashima
K
K
Tanaka
S
S
Kato
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D044842:Cullin Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D000075687:NEDD8 Protein; D011817:Rabbits; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D044764:Ubiquitin-Activating Enzymes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D029701:Saccharomyces cerevisiae Proteins; C112595:UBC12 protein, S cerevisiae; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes; C491802:NAE protein, human