Oxygen-regulated degradation of fission yeast SREBP by Ofd1, a prolyl hydroxylase family member

EMBO J. 2008 May 21;27(10):1491-501. doi: 10.1038/emboj.2008.83. Epub 2008 Apr 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anaerobiosis
  • Humans
  • Molecular Sequence Data
  • Oxygen / metabolism*
  • Procollagen-Proline Dioxygenase / genetics
  • Procollagen-Proline Dioxygenase / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Structure, Tertiary
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sterol Regulatory Element Binding Proteins / genetics
  • Sterol Regulatory Element Binding Proteins / metabolism*


  • Schizosaccharomyces pombe Proteins
  • Sre1 protein, S pombe
  • Sterol Regulatory Element Binding Proteins
  • Procollagen-Proline Dioxygenase
  • Proteasome Endopeptidase Complex
  • Oxygen