Sensing a Need for Oxygen

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Science  08 Apr 2005:
Vol. 308, Issue 5719, pp. 169
DOI: 10.1126/science.308.5719.169b

The sterol regulatory element-binding proteins (SREBPs) are a family of endoplasmic reticulum (ER) membrane-bound transcription factors that, in mammals stimulate the transcription of genes involved in cholesterol and fatty acid synthesis, and are regulated by feedback inhibition. SREBP is activated through proteolytic cleavage in the Golgi; high concentrations of sterols promote formation of a complex between SREBP and the SREBP cleavage-activating protein (SCAP) and the ER protein Insig, which traps SREBP-SCAP in the ER. Hughes et al. identified a gene (sre1+) in fission yeast with sequence similarity to that encoding human SREBP-1a and a similar membrane topology, and also the yeast homologs of SCAP (scp1+) and of Insig-1 (ins1+). Microarray analysis of sterol-depleted wild-type yeast and yeast lacking scp1 indicated that Sre1 promoted the transcription of genes involved in sterol biosynthesis and also that of genes required for the shift from aerobic to anaerobic growth. Yeast lacking sre1 or scp1 were unable to grow in the absence of oxygen, whereas low oxygen stimulated the expression of Sre1 targets in wild-type cells. Shifting yeast to low oxygen reduced ergosterol synthesis; after several hours, wild-type cells were able to adapt and increase ergosterol synthesis, whereas cells lacking sre1 could not. Thus, the authors propose that Sre1 monitors oxygen availability through oxygen-dependent sterol synthesis. — EMA

Cell 120, 831 (2005).

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