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Article: A Role of DNA-PK for the Metabolic Gene Regulation in Response to Insulin

TitleA Role of DNA-PK for the Metabolic Gene Regulation in Response to Insulin
Authors
Issue Date2009
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell
Citation
Cell, 2009, v. 136 n. 6, p. 1056-1072 How to Cite?
AbstractFatty acid synthase (FAS) is a central enzyme in lipogenesis and transcriptionally activated in response to feeding and insulin signaling. The transcription factor USF is required for the activation of FAS transcription, and we show here that USF phosphorylation by DNA-PK, which is dephosphorylated by PP1 in response to feeding, triggers a switch-like mechanism. Under fasting conditions, USF-1 is deacetylated by HDAC9, causing promoter inactivation. In contrast, feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation. DNA break/repair components associated with USF induce transient DNA breaks during FAS activation. In DNA-PK-deficient SCID mice, feeding-induced USF-1 phosphorylation/acetylation, DNA breaks, and FAS activation leading to lipogenesis are impaired, resulting in decreased triglyceride levels. Our study demonstrates that a kinase central to the DNA damage response mediates metabolic gene activation. © 2009 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/183380
ISSN
2015 Impact Factor: 28.71
2015 SCImago Journal Rankings: 28.188
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, RHFen_US
dc.contributor.authorChang, Ien_US
dc.contributor.authorHudak, CSSen_US
dc.contributor.authorHyun, Sen_US
dc.contributor.authorKwan, HYen_US
dc.contributor.authorSul, HSen_US
dc.date.accessioned2013-05-27T07:11:39Z-
dc.date.available2013-05-27T07:11:39Z-
dc.date.issued2009en_US
dc.identifier.citationCell, 2009, v. 136 n. 6, p. 1056-1072en_US
dc.identifier.issn0092-8674en_US
dc.identifier.urihttp://hdl.handle.net/10722/183380-
dc.description.abstractFatty acid synthase (FAS) is a central enzyme in lipogenesis and transcriptionally activated in response to feeding and insulin signaling. The transcription factor USF is required for the activation of FAS transcription, and we show here that USF phosphorylation by DNA-PK, which is dephosphorylated by PP1 in response to feeding, triggers a switch-like mechanism. Under fasting conditions, USF-1 is deacetylated by HDAC9, causing promoter inactivation. In contrast, feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation. DNA break/repair components associated with USF induce transient DNA breaks during FAS activation. In DNA-PK-deficient SCID mice, feeding-induced USF-1 phosphorylation/acetylation, DNA breaks, and FAS activation leading to lipogenesis are impaired, resulting in decreased triglyceride levels. Our study demonstrates that a kinase central to the DNA damage response mediates metabolic gene activation. © 2009 Elsevier Inc. All rights reserved.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cellen_US
dc.relation.ispartofCellen_US
dc.titleA Role of DNA-PK for the Metabolic Gene Regulation in Response to Insulinen_US
dc.typeArticleen_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.cell.2008.12.040en_US
dc.identifier.pmid19303849-
dc.identifier.scopuseid_2-s2.0-62149105212en_US
dc.identifier.volume136en_US
dc.identifier.issue6en_US
dc.identifier.spage1056en_US
dc.identifier.epage1072en_US
dc.identifier.isiWOS:000264403900012-
dc.publisher.placeUnited Statesen_US
dc.identifier.f10001157812-

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