Regulation of sterol carrier protein gene expression by the forkhead transcription factor FOXO3a.
The SCP gene encodes two proteins, sterol carrier protein X (SCPx) and SCP2, that are independently regulated by separate promoters. SCPx has been shown to be the thiolase involved in the breakdown of branched-chain fatty acids and in the biosynthesis of bile acids. The in vivo function of SCP2 however remains to be established. The transcriptional regulation of SCPx and SCP2 is unclear, but their promoter regions contain several putative regulatory domains. We show here that both SCPx and SCP2 are upregulated by the daf-16-like Forkhead transcription factor FOXO3a (also known as FKHRL1) on the level of promoter activity. It was recently described that Forkheads regulate protection against (oxidative) stress in both Caenorhabditis elegans and mammalian cells. We looked into a role for SCP2 in the cellular defense against oxidative damage and found that a fluorescent fatty acid analog bound to SCP2 is protected against H2O2/Cu2+-induced oxidative damage. We propose a model for the way in which SCP2 could protect fatty acids from peroxidation.
Dansen
Tobias B
TB
Department of Biochemistry of Lipids, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. tdansen@cc.ucsf.edu
Kops
Geert J P L
GJ
Denis
Simone
S
Jelluma
Nannette
N
Wanders
Ronald J A
RJ
Bos
Johannes L
JL
Burgering
Boudewijn M T
BM
Wirtz
Karel W A
KW
D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C072087:sterol carrier proteins; D000101:Acetyl-CoA C-Acetyltransferase