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The Hypoxic Regulator of Sterol Synthesis Nro1 Is a Nuclear Import Adaptor

  作者 Yeh, TL; Lee, CYS; Amzel, LM; Espenshade, PJ; Bianchet, MA  
  选自 期刊  Structure;  卷期  2011年19-4;  页码  503-514  
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[摘要]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 angstrom resolution shows an all-alpha-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.

 
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