Abstract
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.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism*
-
Cullin Proteins*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Humans
-
In Vitro Techniques
-
Ligases / genetics
-
Ligases / metabolism
-
Molecular Sequence Data
-
NEDD8 Protein
-
Rabbits
-
Saccharomyces cerevisiae Proteins*
-
Sequence Homology, Amino Acid
-
Ubiquitin-Activating Enzymes
-
Ubiquitin-Protein Ligases
-
Ubiquitins / genetics
-
Ubiquitins / metabolism*
Substances
-
Cell Cycle Proteins
-
Cullin 1
-
Cullin Proteins
-
DNA-Binding Proteins
-
NEDD8 Protein
-
NEDD8 protein, human
-
Saccharomyces cerevisiae Proteins
-
UBC12 protein, S cerevisiae
-
Ubiquitins
-
Ubiquitin-Protein Ligases
-
Ligases
-
Ubiquitin-Activating Enzymes
-
NAE protein, human
Associated data
-
GENBANK/AB012190
-
GENBANK/AB012191
-
GENBANK/AB012193
-
GENBANK/D23662