A CHKA-PML autophagy checkpoint enables tumors to evade glutamine starvation - PubMed
7 hours ago
- #glutamine-deprivation
- #tumor-metabolism
- #autophagy
- Glutamine metabolism is crucial for tumor cell proliferation and biosynthesis.
- Solid tumors often experience chronic glutamine deprivation, requiring adaptive mechanisms.
- Glutamine scarcity upregulates choline kinase alpha (CHKA), enhancing its noncanonical protein kinase activity.
- CHKA phosphorylates promyelocytic leukemia (PML) at tyrosine 339, promoting its cytoplasmic localization.
- Cytoplasmic PML induces SUMOylation of WIPI2, blocking its degradation and increasing autophagic flux.
- This CHKA-PML-WIPI2 axis helps tumor cells survive under metabolic stress.
- The study provides insights into metabolic plasticity and potential therapeutic targets for glutamine-dependent cancers.