Identification of novel genes and pathways regulating SREBP transcriptional activity.

Autor: Sandipan Chatterjee, Joseph D Szustakowski, Nirmala R Nanguneri, Craig Mickanin, Mark A Labow, Axel Nohturfft, Kumlesh K Dev, Rajeev Sivasankaran
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: PLoS ONE, Vol 4, Iss 4, p e5197 (2009)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0005197
Popis: BackgroundLipid metabolism in mammals is orchestrated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs) that control the expression of genes required for the uptake and synthesis of cholesterol, fatty acids, and triglycerides. SREBPs are thus essential for insulin-induced lipogenesis and for cellular membrane homeostasis and biogenesis. Although multiple players have been identified that control the expression and activation of SREBPs, gaps remain in our understanding of how SREBPs are coordinated with other physiological pathways.MethodologyTo identify novel regulators of SREBPs, we performed a genome-wide cDNA over-expression screen to identify proteins that might modulate the transcription of a luciferase gene driven from an SREBP-specific promoter. The results were verified through secondary biological assays and expression data were analyzed by a novel application of the Gene Set Enrichment Analysis (GSEA) method.Conclusions/significanceWe screened 10,000 different cDNAs and identified a number of genes and pathways that have previously not been implicated in SREBP control and cellular cholesterol homeostasis. These findings further our understanding of lipid biology and should lead to new insights into lipid associated disorders.
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