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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-?-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.

SUBMITTER: Yeh TL

PROVIDER: S-EPMC3086001 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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

Yeh Tzu-Lan TL Lee Chih-Yung S CY Amzel L Mario LM Espenshade Peter J PJ Bianchet Mario A MA

Structure (London, England : 1993) 20110401 4

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 ...[more]

PMID: 21481773

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