A new NEDD8-ligating system for cullin-4A
- Fumio Osaka1,
- Hiroshi Kawasaki2,
- Noriko Aida1,
- Mihoro Saeki1,
- Tomoki Chiba3,
- Seiichi Kawashima2,
- Keiji Tanaka3, and
- Seishi Kato1,4
- 1Kato Cytoprotein Network Project, ERATO, Japan Science and Technology Corporation (JST), Sagami Chemical Research Center, Sagamihara, Kanagawa 229-0012, Japan; 2The Tokyo Metropolitan Institute of Medical Science, and 3CREST, Japan Science and Technology Corporation (JST), Bunkyo-ku, Tokyo 113-0021, Japan
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.
Keywords
Footnotes
-
↵4 Corresponding author.
-
E-MAIL seishi{at}sagami.or.jp; FAX 81-427-49-7631.
-
- Received April 10, 1998.
- Accepted May 27, 1998.
- Cold Spring Harbor Laboratory Press
