The hypoxic regulator of sterol synthesis Nro1 is a nuclear import adaptor

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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.

Original languageEnglish (US)
Pages (from-to)503-514
Number of pages12
JournalStructure
Volume19
Issue number4
DOIs
StatePublished - Apr 13 2011

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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