The cyclomodulin CIF alters cullin neddylation dynamics.
The bacterial effector protein CIF converts glutamine 40 of NEDD8 to glutamate (Q40E), causing cytopathic effects and inhibiting cell proliferation. Although these have been attributed to blocking the functions of cullin-RING ubiquitin ligases (CRLs), how CIF modulates NEDD8-dependent signaling is unclear. Here, we use conditional NEDD8-dependent yeast to explore the ... effects of CIF on cullin neddylation. Although CIF causes cullin deneddylation and the generation of free NEDD8 Q40E, inhibiting the COP9 signalosome (CSN) allows Q40E to form only on NEDD8 attached to cullins. In the presence of CSN, NEDD8 Q40E is removed from cullins more rapidly than NEDD8, leading to a decrease in steady-state cullin neddylation. As NEDD8 Q40E is competent for cullin conjugation in the absence of functional CSN and with over-expression of the NEDD8 ligase Dcn1, our data are consistent with NEDD8 deamidation causing enhanced deneddylation of cullins by CSN. This leads to a dramatic change in the extent of activated CRLs.
J. Biol. Chem.
Date: Apr. 15, 2013
PubMed ID: 23589306
View in: Pubmed Google Scholar
Download Curated Data For This Publication
154721
Switch View:
- Interactions 1