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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

Authors

  • Yeh TL
  • Lee CY
  • Amzel LM
  • Espenshade PJ
  • Bianchet MA

Journal

Structure (London, England : 1993)

Publication Data

April 13, 2011

Associated Grants

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

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