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EMBO Rep. 2002 Feb;3(2):177-82. Epub 2002 Jan 29.

An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells.

Author information

1
Department of Adult Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Skp1-Cdc53/Cul1-F-box (SCF) complexes constitute a class of E3 ubiquitin ligases. Recently, a multiprotein complex containing pVHL, elongin C and Cul2 (VEC) was shown to structurally and functionally resemble SCF complexes. Cdc53 and the Cullins can become covalently linked to the ubiquitin-like molecule Rub1/NEDD8. Inhibition of neddylation inhibits SCF function in vitro and in yeast and plants. Here we show that ongoing neddylation is likewise required for VEC function in vitro and for the degradation of SCF and VEC targets in mammalian cells. Thus, neddylation regulates the activity of two specific subclasses of mammalian ubiquitin ligases.

PMID:
11818338
PMCID:
PMC1083969
DOI:
10.1093/embo-reports/kvf028
[Indexed for MEDLINE]
Free PMC Article

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