title: Protection from bacterial-toxin-induced apoptosis in macrophages requires the lipogenic transcription factor sterol regulatory element binding protein 1a.
abstract: Sterol regulatory element binding protein (SREBP) transcription factors activate genes of lipid metabolism, but recent studies indicate they also activate genes involved in other physiologic processes, suggesting that SREPBs have evolved to connect lipid metabolism with diverse physiologic responses. There are three major mammalian SREBPs, and the 1a isoform is specifically expressed at very high levels in macrophages, where a recent study showed that it couples lipid synthesis to the proinflammatory phase of the innate immune response. In the present study, we show that loss of SREBP-1a also results in an increase in apoptosis after exposure to bacterial pore-forming toxins and we show this is a result of a selective reduction in the expression of the gene coding for the antiapoptotic factor apoptosis inhibitor 6 (Api6). Additional studies demonstrate that SREBP-1a specifically activates the Api6 gene through a binding site in its proximal promoter, thus establishing the Api6 gene as a newly identified SREBP-1a target gene.
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Dalseo-Gu, Daegu, South Korea.
authors.forename: Seung-Soon
authors.initials: SS
authors.lastname: Im
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Osborne
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology; D001665:Binding Sites; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000187:drug effects; D050356:Lipid Metabolism / Q000235:genetics; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D001427:Bacterial Toxins; C117272:Cd5l protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051780:Sterol Regulatory Element Binding Protein 1