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

Weibo Luo, Benjamin Lin, Yingfei Wang, Jun Zhong, Robert O'Meally, Robert N. Cole, Akhilesh Pandey, Andre Levchenko, Gregg L. Semenza

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2788-2796
Number of pages9
JournalMolecular Biology of the Cell
Volume25
Issue number18
DOIs
StatePublished - Sep 15 2014

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Hydroxylation
Polymerization
Cell Movement
Actins
Post Translational Protein Processing
Actin Cytoskeleton
2-oxoglutarate 3-dioxygenase proline
Proline
Small Interfering RNA
Pharmacology

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

PHD3-mediated prolyl hydroxylation of nonmuscle actin impairs polymerization and cell motility. / Luo, Weibo; Lin, Benjamin; Wang, Yingfei; Zhong, Jun; O'Meally, Robert; Cole, Robert N.; Pandey, Akhilesh; Levchenko, Andre; Semenza, Gregg L.

In: Molecular Biology of the Cell, Vol. 25, No. 18, 15.09.2014, p. 2788-2796.

Research output: Contribution to journalArticle

Luo, W, Lin, B, Wang, Y, Zhong, J, O'Meally, R, Cole, RN, Pandey, A, Levchenko, A & Semenza, GL 2014, 'PHD3-mediated prolyl hydroxylation of nonmuscle actin impairs polymerization and cell motility', Molecular Biology of the Cell, vol. 25, no. 18, pp. 2788-2796. https://doi.org/10.1091/mbc.E14-02-0775
Luo, Weibo ; Lin, Benjamin ; Wang, Yingfei ; Zhong, Jun ; O'Meally, Robert ; Cole, Robert N. ; Pandey, Akhilesh ; Levchenko, Andre ; Semenza, Gregg L. / PHD3-mediated prolyl hydroxylation of nonmuscle actin impairs polymerization and cell motility. In: Molecular Biology of the Cell. 2014 ; Vol. 25, No. 18. pp. 2788-2796.
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