CHD4 regulates PADI1 and PADI3 expression linking pyruvate kinase M2 citrullination to glycolysis and proliferation [article]

Irwin Davidson, Sebastien Coassolo, Guillaume Davidson, Luc Negroni, Giovanni Gambi, Sylvain Daujat, Christophe Romier
2019 bioRxiv   pre-print
The CHD4 subunit of the Nucleosome Remodelling and Deacetylation (NuRD) complex regulates expression of PADI1 (Protein Arginine Deiminase 1) and PADI3 in multiple cancer cell types modulating citrullination of three arginines of the allosterically-regulated glycolytic enzyme pyruvate kinase M2 (PKM2). PKM2 citrullination lowers its sensitivity to the inhibitors Tryptophan, Alanine and Phenylalanine shifting the equilibrium towards the activator Serine bypassing normal physiological regulation
more » ... ogical regulation by low Serine levels and promoting excessive glycolysis, lowered intracellular ATP and slowed proliferation. Our data provide unique insight as to how conversion of arginines to citrulline impacts key interactions within PKM2 adding another layer of complexity to the mechanisms that regulate the activity of this important enzyme.
doi:10.1101/718486 fatcat:45vjhxwg3rgejmyyne3pcps4su