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Published on: March 14, 2019
NEDD8 recruits E2-ubiquitin to SCF E3 ligase
T Kawakami1, T Chiba, T Suzuki
1Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
The EMBO Journal
|August 3, 2001
Summary
NEDD8 modification of cullin-1 enhances the recruitment of Ub-conjugating enzyme Ubc4 to the SCF complex. This accelerates E2-E3 complex formation, stimulating protein polyubiquitylation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Signaling
Background:
- NEDD8/Rub1 is a ubiquitin-like modifier attached to cullin proteins.
- NEDD8 enhances the SCF complex's ubiquitylating activity, but the mechanism is unclear.
Purpose of the Study:
- To elucidate the mechanistic role of NEDD8 modification in SCF complex activity.
Main Methods:
- In vitro reconstitution of the SCF complex and associated factors.
- Analysis of Ub-conjugating enzyme (E2) recruitment to the SCF complex (E3).
Main Results:
- NEDD8 modification of cullin-1 significantly enhances Ubc4 (E2) recruitment to the SCF complex (E3).
- This enhanced recruitment is dependent on the thioester linkage of ubiquitin to Ubc4.
- The NEDD8 system accelerates E2-E3 complex formation.
Conclusions:
- NEDD8 modification of cullin-1 is a key regulatory step that enhances SCF complex ubiquitin ligase activity.
- The findings provide a mechanistic explanation for how NEDD8 stimulates polyubiquitylation.
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