Stabilizing HIF-1α by citrullination promotes tumor progression
Citrullination role in regulating tumor progression is not well understood.
The researchers show that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization and stabilized HIF-1α blocks von Hippel-Lindau (VHL) binding, thereby antagonizing HIF-1α ubiquitination and subsequent proteasome degradation.
We also show that citrullinated HIF-1αR698, HIF-1α and PADI4 are highly expressed in hepatocellular carcinoma (HCC) tumor tissues.
The researchers demonstrate that that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4 and suppresses tumor progression.
