TY - JOUR
T1 - The SREBP pathway in Drosophila
T2 - Regulation by palmitate, not sterols
AU - Seegmiller, Adam C.
AU - Dobrosotskaya, Irina
AU - Goldstein, Joseph L.
AU - Ho, Y. K.
AU - Brown, Michael S.
AU - Rawson, Robert B.
N1 - Funding Information:
We thank Lisa Beatty for invaluable help with tissue culture, Jeff Cormier for DNA sequencing, and Deborah Morgan and Jae Myoung Suh for excellent technical assistance. This work was supported by grants from the National Institutes of Health (NIH; HL-20948), the American Heart Association (0130010N), the Perot Family Foundation, and the W.M. Keck Foundation. A.C.S. is supported by NIH Medical Scientist Training grant GM08014.
PY - 2002/2
Y1 - 2002/2
N2 - In mammals, synthesis of cholesterol and unsaturated fatty acids is controlled by SREBPs, a family of membrane-bound transcription factors. Here, we show that the Drosophila genome encodes all components of the SREBP pathway, including a single SREBP (dSREBP), SREBP cleavage-activating protein (dSCAP), and the two proteases that process SREBP at sites 1 and 2 to release the nuclear fragment. In cultured Drosophila S2 cells, dSREBP is processed at sites 1 and 2, and the liberated fragment increases mRNAs encoding enzymes of fatty acid biosynthesis, but not sterol or isoprenoid biosynthesis. Processing requires dSCAP, but is not inhibited by sterols as in mammals. Instead, dSREBP processing is blocked by palmitic acid. These findings suggest that the ancestral SREBP pathway functions to maintain membrane integrity rather than to control cholesterol homeostasis.
AB - In mammals, synthesis of cholesterol and unsaturated fatty acids is controlled by SREBPs, a family of membrane-bound transcription factors. Here, we show that the Drosophila genome encodes all components of the SREBP pathway, including a single SREBP (dSREBP), SREBP cleavage-activating protein (dSCAP), and the two proteases that process SREBP at sites 1 and 2 to release the nuclear fragment. In cultured Drosophila S2 cells, dSREBP is processed at sites 1 and 2, and the liberated fragment increases mRNAs encoding enzymes of fatty acid biosynthesis, but not sterol or isoprenoid biosynthesis. Processing requires dSCAP, but is not inhibited by sterols as in mammals. Instead, dSREBP processing is blocked by palmitic acid. These findings suggest that the ancestral SREBP pathway functions to maintain membrane integrity rather than to control cholesterol homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=0036480346&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036480346&partnerID=8YFLogxK
U2 - 10.1016/S1534-5807(01)00119-8
DO - 10.1016/S1534-5807(01)00119-8
M3 - Article
C2 - 11832248
AN - SCOPUS:0036480346
SN - 1534-5807
VL - 2
SP - 229
EP - 238
JO - Developmental cell
JF - Developmental cell
IS - 2
ER -