title: The hypoxic regulator of sterol synthesis nro1 is a nuclear import adaptor.
abstract: 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.
authors.affiliation: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Tzu-Lan
authors.initials: TL
authors.lastname: Yeh
authors.forename: Chih-Yung S
authors.initials: CY
authors.lastname: Lee
authors.forename: L Mario
authors.initials: LM
authors.lastname: Amzel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Espenshade
authors.forename: Mario A
authors.initials: MA
authors.lastname: Bianchet
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000693:Anaerobiosis; D002467:Cell Nucleus / Q000378:metabolism*; D018360:Crystallography, X-Ray; D047468:Immunoprecipitation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013261:Sterols / Q000096:biosynthesis*; D020798:Two-Hybrid System Techniques
chemical_list: C559983:Nro1 protein, S pombe; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C500467:Sre1 protein, S pombe; D013261:Sterols; D011393:Procollagen-Proline Dioxygenase; D010100:Oxygen