PHD3-mediated prolyl hydroxylation of nonmuscle actin impairs polymerization and cell motility

Mol Biol Cell. 2014 Sep 15;25(18):2788-96. doi: 10.1091/mbc.E14-02-0775. Epub 2014 Jul 30.


Actin filaments play an essential role in cell movement, and many posttranslational modifications regulate actin filament assembly. Here we report that prolyl hydroxylase 3 (PHD3) interacts with nonmuscle actin in human cells and catalyzes hydroxylation of actin at proline residues 307 and 322. Blocking PHD3 expression or catalytic activity by short hairpin RNA knockdown or pharmacological inhibition, respectively, decreased actin prolyl hydroxylation. PHD3 knockdown increased filamentous F-actin assembly, which was reversed by PHD3 overexpression. PHD3 knockdown increased cell velocity and migration distance. Inhibition of PHD3 prolyl hydroxylase activity by dimethyloxalylglycine also increased actin polymerization and cell migration. These data reveal a novel role for PHD3 as a negative regulator of cell motility through posttranslational modification of nonmuscle actins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Cell Movement*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hydroxylation
  • Hypoxia-Inducible Factor-Proline Dioxygenases / physiology*
  • Molecular Sequence Data
  • Polymerization
  • Proline / metabolism
  • Protein Multimerization
  • Protein Processing, Post-Translational


  • Actins
  • Proline
  • EGLN3 protein, human
  • Hypoxia-Inducible Factor-Proline Dioxygenases