Identification of novel genes and pathways regulating SREBP transcriptional activity.

<h4>Background</h4>Lipid 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...

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Autores principales: Sandipan Chatterjee, Joseph D Szustakowski, Nirmala R Nanguneri, Craig Mickanin, Mark A Labow, Axel Nohturfft, Kumlesh K Dev, Rajeev Sivasankaran
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Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/f9c070563cbb4b3cb0db1a17be7bb0ba
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spelling oai:doaj.org-article:f9c070563cbb4b3cb0db1a17be7bb0ba2021-11-25T06:16:03ZIdentification of novel genes and pathways regulating SREBP transcriptional activity.1932-620310.1371/journal.pone.0005197https://doaj.org/article/f9c070563cbb4b3cb0db1a17be7bb0ba2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19381295/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Lipid 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.<h4>Methodology</h4>To 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.<h4>Conclusions/significance</h4>We 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.Sandipan ChatterjeeJoseph D SzustakowskiNirmala R NanguneriCraig MickaninMark A LabowAxel NohturfftKumlesh K DevRajeev SivasankaranPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5197 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sandipan Chatterjee
Joseph D Szustakowski
Nirmala R Nanguneri
Craig Mickanin
Mark A Labow
Axel Nohturfft
Kumlesh K Dev
Rajeev Sivasankaran
Identification of novel genes and pathways regulating SREBP transcriptional activity.
description <h4>Background</h4>Lipid 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.<h4>Methodology</h4>To 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.<h4>Conclusions/significance</h4>We 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.
format article
author Sandipan Chatterjee
Joseph D Szustakowski
Nirmala R Nanguneri
Craig Mickanin
Mark A Labow
Axel Nohturfft
Kumlesh K Dev
Rajeev Sivasankaran
author_facet Sandipan Chatterjee
Joseph D Szustakowski
Nirmala R Nanguneri
Craig Mickanin
Mark A Labow
Axel Nohturfft
Kumlesh K Dev
Rajeev Sivasankaran
author_sort Sandipan Chatterjee
title Identification of novel genes and pathways regulating SREBP transcriptional activity.
title_short Identification of novel genes and pathways regulating SREBP transcriptional activity.
title_full Identification of novel genes and pathways regulating SREBP transcriptional activity.
title_fullStr Identification of novel genes and pathways regulating SREBP transcriptional activity.
title_full_unstemmed Identification of novel genes and pathways regulating SREBP transcriptional activity.
title_sort identification of novel genes and pathways regulating srebp transcriptional activity.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/f9c070563cbb4b3cb0db1a17be7bb0ba
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