Citrullination modulation stabilizes HIF-1α to promote tumour progression.

ABSTRACT: Citrullination plays an essential role in various physiological or pathological processes, however, whether citrullination is involved in regulating tumour progression and the potential therapeutic significance have not been well explored. Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Mechanistically, PADI4-mediated HIF-1α^R698 citrullination blocks von Hippel-Lindau (VHL) binding, thereby antagonizing HIF-1α ubiquitination and subsequent proteasome degradation. We also show that citrullinated HIF-1α^R698, HIF-1α and PADI4 are highly expressed in hepatocellular carcinoma (HCC) tumour tissues, suggesting a potential correlation between PADI4-

SUBMITTER: Chen R 

PROVIDER: S-EPMC11372217 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature