Abstract 525: PHD3-mediated prolyl hydroxylation of non-muscle actin impairs polymerization and cell motility

Abstract

Abstract Actin filaments play an essential role in cell movement and many post-translational modifications regulate actin filament assembly. Here we report that prolyl hydroxylase 3 (PHD3) interacts with non-muscle actin in human cells and catalyzes hydroxylation of actin at proline residues 307 and 322. Blocking PHD3 catalytic activity, by either a pharmacological inhibitor or short hairpin RNA knockdown of PHD3 expression, decreases actin prolyl hydroxylation. Knockdown of PHD3 significantly increases filamentous F-actin assembly, which is reversed by PHD3 overexpression. PHD3 knockdown significantly increases cell velocity and migration distance. Inhibition of PHD3 prolyl hydroxylase activity by dimethyloxalylglycine also increases actin polymerization and cell migration. These data reveal a novel role for PHD3 as a negative regulator of cell motility through post-translational modification of non-muscle actins. Citation Format: Weibo Luo, Gregg L. Semenza. PHD3-mediated prolyl hydroxylation of non-muscle actin impairs polymerization and cell motility. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 525. doi:10.1158/1538-7445.AM2015-525