Non–SCF-type F-box protein Roy1 interacts with the Rab5-like small GTPase Ypt52. Skp1 is indispensable for the interaction of Roy1 and Ypt52. Roy1 binds to GDP and the nucleotide-free form of Ypt52 and inhibits the formation of GTP-bound, active Ypt52. Roy1 negatively modulates cell viability and intracellular transport by suppressing Ypt52.

Background: How the function of Rab5 isoforms is regulated remains unclear. Results: The third Rab5 isoform, Ypt53, is up-regulated significantly under nutrient stress. Conclusion:The up-regulated Ypt53 and the constitutive Vps21 are crucial for vesicle transport and vacuolar hydrolase activity, and they prevent ROS accumulation and mitochondrial dysfunction. Significance: The function of three Rab5 isoforms may be regulated differently to adapt to environmental changes.