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Norway

PMID:24550447  

OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation.

Rachelle S Singleton | Phebee Liu-Yi | Fabio Formenti | Wei Ge | Rok Sekirnik | Roman Fischer | Julie Adam | Patrick J Pollard | Alexander Wolf | Armin Thalhammer | Christoph Loenarz | Emily Flashman | Atsushi Yamamoto | Mathew L Coleman | Benedikt M Kessler | Pablo Wappner | Christopher J Schofield | Peter J Ratcliffe | Matthew E Cockman
Proceedings of the National Academy of Sciences of the United States of America | 2014

2-Oxoglutarate (2OG) and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1) is predicted to be a conserved 2OG oxygenase, the catalytic domain of which is related to hypoxia-inducible factor prolyl hydroxylases. OGFOD1 homologs in yeast are implicated in diverse cellular functions ranging from oxygen-dependent regulation of sterol response genes (Ofd1, Schizosaccharomyces pombe) to translation termination/mRNA polyadenylation (Tpa1p, Saccharomyces cerevisiae). However, neither the biochemical activity of OGFOD1 nor the identity of its substrate has been defined. Here we show that OGFOD1 is a prolyl hydroxylase that catalyzes the posttranslational hydroxylation of a highly conserved residue (Pro-62) in the small ribosomal protein S23 (RPS23). Unusually OGFOD1 retained a high affinity for, and forms a stable complex with, the hydroxylated RPS23 substrate. Knockdown or inactivation of OGFOD1 caused a cell type-dependent induction of stress granules, translational arrest, and growth impairment in a manner complemented by wild-type but not inactive OGFOD1. The work identifies a human prolyl hydroxylase with a role in translational regulation.

Pubmed ID: 24550447

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
  • Agency: British Heart Foundation, United Kingdom
    Id: PG/12/33/29546
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K010816/1
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/11/1/28684

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International Mouse Phenotyping Consortium (IMPC) (tool)

RRID:SCR_006158

Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.

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