|
 |
|
|
|
EMBO reports 9, 5, 486–491 (2008)
doi:10.1038/embor.2008.19
AOP Published online: 7 March 2008
NEDD8 acts as a 'molecular switch' defining the functional selectivity of VHL
Ryan C Russell & Michael Ohh
|
|
|
|
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
To whom correspondence should be addressed
Michael Ohh Tel: +1 416 946 7922; Fax: +1 416 978 5959; E-mail: michael.ohh@utoronto.ca
Received 8 October 2007; Accepted 23 January 2008; Published online 7 March 2008.
|
|
|
|
Abstract
The von Hippel–Lindau (VHL) tumour suppressor protein is important in the E3 ubiquitin ligase ECV (Elongin B/C–CUL2–VHL)-mediated destruction of hypoxia-inducible factor and the promotion of fibronectin (FN) extracellular matrix assembly. Although the precise molecular mechanism controlling the selectivity of VHL function remains unknown, a failure in either process is associated with oncogenic progression. Here, we show that VHL performs its FN-associated function independently of the ECV complex, highlighting the autonomy of these pathways. Furthermore, we show that NEDD8, a ubiquitin-like molecule, acts as a 'molecular switch' in which its covalent conjugation to VHL prohibits the engagement of the scaffold component CUL2 and, concomitantly, activates the association with FN. These findings provide the first mechanistic step in defining the functional selectivity of VHL and explain a previously unrecognized function of NEDD8.
|
 |
|
Top of page MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated | |
|
top  |
|
|
|
