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An intact NEDD8 pathway is required for Cullin‐dependent ubiquitylation in mammalian cells
Author(s) -
Ohh Michael,
Kim William Y,
Moslehi Javid J,
Chen Yuzhi,
Chau Vincent,
Read Margaret A,
Kaelin William G
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf028
Subject(s) - nedd8 , neddylation , cullin , ubiquitin , skp1 , microbiology and biotechnology , ubiquitin ligase , function (biology) , biology , in vitro , f box protein , biochemistry , chemistry , gene
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.