TY - JOUR
T1 - SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast
AU - Hughes, Adam L.
AU - Todd, Bridget L.
AU - Espenshade, Peter J.
N1 - Funding Information:
From UT-Southwestern Medical Center at Dallas, we are deeply grateful to Dr. Joseph Goldstein and Dr. Michael Brown for their expert guidance and training. We thank Norma Anderson, Tammy Dinh, and Richard Gibson for excellent technical assistance. From Johns Hopkins, we thank Raymond Chai and Anuradha Gokhale for outstanding technical assistance. This work was supported by a grant from the National Insitutes of Health (HL-077588) (to P.E.). A.L.H. and B.L.T. are supported by NIH training grant GM007445. P.J.E. is a recipient of a Burroughs Wellcome Fund Career Award in the Biomedical Sciences.
PY - 2005/3/25
Y1 - 2005/3/25
N2 - Cholesterol and fatty acid synthesis in mammals are controlled by SREBPs, a family of membrane bound transcription factors. Our studies identified homologs of SREBP, its binding partner SCAP, and the ER retention protein Insig in Schizosaccharomyces pombe, named sre1+, scp1+, and ins1+. Like SREBP, Sre1 is cleaved and activated in response to sterol depletion in a Scp1-dependent manner. Microarray analysis revealed that Sre1 activates sterol biosynthetic enzymes as in mammals, and, surprisingly, Sre1 also stimulates transcription of genes required for adaptation to hypoxia. Furthermore, Sre1 rapidly activates these target genes in response to low oxygen and is itself required for anaerobic growth. Based on these findings, we propose and test a model in which Sre1 and Scp1 monitor oxygen-dependent sterol synthesis as an indirect measure of oxygen supply and mediate a hypoxic response in fission yeast.
AB - Cholesterol and fatty acid synthesis in mammals are controlled by SREBPs, a family of membrane bound transcription factors. Our studies identified homologs of SREBP, its binding partner SCAP, and the ER retention protein Insig in Schizosaccharomyces pombe, named sre1+, scp1+, and ins1+. Like SREBP, Sre1 is cleaved and activated in response to sterol depletion in a Scp1-dependent manner. Microarray analysis revealed that Sre1 activates sterol biosynthetic enzymes as in mammals, and, surprisingly, Sre1 also stimulates transcription of genes required for adaptation to hypoxia. Furthermore, Sre1 rapidly activates these target genes in response to low oxygen and is itself required for anaerobic growth. Based on these findings, we propose and test a model in which Sre1 and Scp1 monitor oxygen-dependent sterol synthesis as an indirect measure of oxygen supply and mediate a hypoxic response in fission yeast.
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U2 - 10.1016/j.cell.2005.01.012
DO - 10.1016/j.cell.2005.01.012
M3 - Article
C2 - 15797383
AN - SCOPUS:17644401005
SN - 0092-8674
VL - 120
SP - 831
EP - 842
JO - Cell
JF - Cell
IS - 6
ER -