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Oxygen‐regulated degradation of fission yeast SREBP by Ofd1, a prolyl hydroxylase family member
Author(s) -
Hughes Bridget T,
Espenshade Peter J
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.83
Subject(s) - biology , yeast , oxygen , fission , family member , biochemistry , microbiology and biotechnology , chemistry , physics , organic chemistry , medicine , family medicine , quantum mechanics , neutron
Sre1, the fission yeast sterol regulatory element binding protein, is an endoplasmic reticulum membrane‐bound transcription factor that responds to changes in oxygen‐dependent sterol synthesis as an indirect measure of oxygen availability. Under low oxygen, Sre1 is proteolytically cleaved and the released N‐terminal transcription factor (Sre1N) activates gene expression essential for hypoxic growth. Here, we describe an oxygen‐dependent mechanism for regulation of Sre1 that is independent of sterol‐regulated proteolysis. Using yeast expressing only Sre1N, we show that Sre1N turnover is regulated by oxygen. Ofd1, an uncharacterized prolyl 4‐hydroxylase‐like 2‐oxoglutarate‐Fe(II) dioxygenase, accelerates Sre1N degradation in the presence of oxygen. However, unlike the prolyl 4‐hydroxylases that regulate mammalian hypoxia‐inducible factor, Ofd1 uses multiple domains to regulate Sre1N degradation by oxygen; the Ofd1 N‐terminal dioxygenase domain is required for oxygen sensing and the Ofd1 C‐terminal domain accelerates Sre1N degradation. Our data support a model whereby the Ofd1 N‐terminal dioxygenase domain is an oxygen sensor that regulates the activity of the C‐terminal degradation domain.