Abstract B010: VHL inhibits autophagy and tumor development by modulating ATG14 hydroxylation in a PHD1-dependent manner

Key Points

• The research explores VHL's role in autophagy regulation and its tumor-suppressive function in clear-cell renal cell carcinoma (ccRCC).
• Analyzed VHL-RCC samples
• Studied molecular interactions between VHL and autophagy regulators
• Identified hydroxylation of ATG14 at Proline 54 by PHD1
• Assessed effects of ATG14 mutations on autophagy inhibition
• VHL suppresses autophagy under nutrient stress
• In ccRCC with non-functional VHL, autophagy is elevated with negative patient outcomes
• VHL binds to hydroxylated ATG14, preventing autophagy initiation
• P54A mutation in ATG14 eliminates VHL's autophagy inhibition
• Combination treatment reduced tumor growth in VHL-deficient mouse models