An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells.
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.
Ohh
Michael
M
Department of Adult Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kim
William Y
WY
Moslehi
Javid J
JJ
Chen
Yuzhi
Y
Chau
Vincent
V
Read
Margaret A
MA
Kaelin
William G
WG
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D044842:Cullin Proteins; D000075065:Elongin; D006801:Humans; D051379:Mice; D000075687:NEDD8 Protein; D010453:Peptide Synthases / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
C105153:CUL2 protein, human; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; C000616395:ELOC protein, human; C000616411:Eloc protein, mouse; D000075065:Elongin; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; C513172:Nedd8 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D010453:Peptide Synthases