Deubiquitinase USP13 regulates glycolytic reprogramming and progression in osteosarcoma by stabilizing METTL3/m⁶A/ATG5 axis.

ABSTRACT: Reprogramming metabolism is a hallmark of cancer cells for rapid progression. However, the detailed functional role of deubiquitinating enzymes (DUBs) in tumor glycolytic reprogramming is still unknown and requires further investigation. USP13 was found to upregulate in osteosarcoma (OS) specimens and promote OS progression through regulating aerobic glycolysis. Interestingly, the m⁶A writer protein, METTL3, has been identified as a novel target of USP13. USP13 interacts with, deubiquitinates, and therefore stabilizes METTL3 at K488 by removing K48-linked ubiquitin chains. Since METTL3 is a well-known m⁶A writer and USP13 stabilizes METTL3, we further found that USP13 increased global m⁶A abundance in OS cells. The results of RNA sequencing and methylated R

SUBMITTER: Wang C 

PROVIDER: S-EPMC10158027 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature