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

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

Author information

1
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
2
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
3
Neuroregeneration Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
4
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
5
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
6
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 gsemenza@jhmi.edu.

Abstract

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.

PMID:
25079693
PMCID:
PMC4161513
DOI:
10.1091/mbc.E14-02-0775
[Indexed for MEDLINE]
Free PMC Article
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