A NEW NEDD8-LIGATING SYSTEM FOR CULLIN-4A

NEDD8 is a ubiquitin (Ub)-like protein. Here we report a novel ubiquit inylation-related pathway for modification by NEDD8. NEDD8 was activat ed by an El (Ub-activating enzyme)-like complex, consisting of APP-BP1 and hUba3 with high respective homologies to the amino-and carboxy-te rminal regions of El and then linked to hUbc12 (a human homolog of yea st 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 o f human cullin/Cdc53 proteins functioning as an essential component of a multifunctional Ub-protein ligase E3 complex that has a critical ro le in Ub-mediated proteolysis.