期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 11, 页码 4031-4036出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1314482111
关键词
translational control; ribosome; 2-oxoglutarate oxygenase; hypoxia
资金
- China Scholarship Council Award
- European Molecular Biology Organization long-term fellowship
- Biotechnology and Biological Sciences Research Council
- Wellcome Trust
- Ludwig Institute for Cancer Research
- Biotechnology and Biological Sciences Research Council [BB/J003018/1, BB/L004275/1] Funding Source: researchfish
- British Heart Foundation [PG/12/33/29546, RG/11/1/28684] Funding Source: researchfish
- Cancer Research UK [18245] Funding Source: researchfish
- Medical Research Council [MR/K010816/1] Funding Source: researchfish
- BBSRC [BB/L004275/1, BB/J003018/1] Funding Source: UKRI
- MRC [MR/K010816/1] Funding Source: UKRI
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.
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