P53-induced RNA-binding protein ZMAT3 inhibits transcription of a hexokinase to suppress mitochondrial respiration.

ABSTRACT: The tumor suppressor p53 is a transcription factor that controls the expression of hundreds of genes. Emerging evidence suggests that the p53-induced RNA-binding protein ZMAT3 is a key splicing regulator that functions in p53-dependent tumor suppression in vitro and in vivo . However, the mechanism by which ZMAT3 functions in the p53 pathway is largely unclear. Here, we discovered a function of ZMAT3 in inhibiting transcription of HKDC1 , a hexokinase that regulates glucose metabolism and mitochondrial respiration. Using quantitative proteomics, we identified HKDC1 as the most significantly upregulated protein in ZMAT3 -depleted colorectal cancer cells. ZMAT3 depletion results in increased mitochondrial respiration that was rescued upon depletion of HK

SUBMITTER: Kumar R 

PROVIDER: S-EPMC12087986 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature