RIT1 oncoproteins escape LZTR1-mediated proteolysis

Defective degradation as disease mechanism Ubiquitination often targets proteins for destruction. Castelet al. describe a mechanism by which mutations in the small guanine triphosphatase RIT1 may act to cause certain developmental disorders and cancers. They detected a protein, LZTR1, that interacted with wild-type RIT1 but not with oncogenic mutant forms of RIT1. LZTR1 acts as a substrate-specific adaptor for a ubiquitin ligase. Altered forms of RIT1 that are not subject to ubiquitin-mediated degradation thus accumulate. Because RIT1 functions in growth factor signaling and excessive signaling, these findings may explain the malignancies associated with RIT1 mutations.Science , this issue p.1226