The mechanism of activation of the Cullin-RING E3 ubiquitin ligases by Nedd8

Activation of the Cullin-RING E3 ubiquitin ligases (CRLs) requires Nedd8, an Ub-like protein, which acts to covalently modify CRL’s cullin subunit. Aside from its fundamental importance to the control of protein stability, Nedd8 has emerged as an effective target in anti-cancer efforts. Our research interests are to understand the function of Nedd8 in enhancing CRL-mediated proteolytic activity in both conformation dependent and independent fashion.