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The hypoxic regulator of sterol synthesis nro1 is a nuclear import adaptor.

Fission yeast protein Sre1, the homolog of the mammalian sterol regulatory element-binding protein (SREBP), is a hypoxic transcription factor required for sterol homeostasis and low-oxygen growth. Nro1 regulates the stability of the N-terminal transcription factor domain of Sre1 (Sre1N) by inhibiting the action of the prolyl 4-hydroxylase-like Ofd1 in an oxygen-dependent manner. The crystal structure of Nro1 determined at 2.2 Å resolution shows an all-α-helical fold that can be divided into two domains: a small N-terminal domain, and a larger C-terminal HEAT-repeat domain. Follow-up studies showed that Nro1 defines a new class of nuclear import adaptor that functions both in Ofd1 nuclear localization and in the oxygen-dependent inhibition of Ofd1 to control the hypoxic response.

Pubmed ID: 21481773 RIS Download

Mesh terms: Active Transport, Cell Nucleus | Amino Acid Sequence | Anaerobiosis | Cell Nucleus | Crystallography, X-Ray | Immunoprecipitation | Models, Molecular | Molecular Sequence Data | Mutation | Nuclear Proteins | Oxygen | Procollagen-Proline Dioxygenase | Protein Binding | Protein Structure, Secondary | Schizosaccharomyces pombe Proteins | Sequence Homology, Amino Acid | Sterols | Two-Hybrid System Techniques

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Associated grants

  • Agency: NHLBI NIH HHS, Id: HL-077588
  • Agency: NIDDK NIH HHS, Id: P30 DK079637
  • Agency: NINDS NIH HHS, Id: R01 NS061827
  • Agency: NHLBI NIH HHS, Id: R01 HL077588
  • Agency: NINDS NIH HHS, Id: R01 NS061827-01A2
  • Agency: NHLBI NIH HHS, Id: R01 HL077588-08
  • Agency: NINDS NIH HHS, Id: 1R01NS061827

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