The SMILE transcriptional corepressor inhibits cAMP response element-binding protein (CREB)-mediated transactivation of gluconeogenic genes
DC Field | Value | Language |
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dc.contributor.author | Lee, Ji-Min | - |
dc.contributor.author | Han, Hye-Sook | - |
dc.contributor.author | Jung, Yoon Seok | - |
dc.contributor.author | Harris, Robert A. | - |
dc.contributor.author | Koo, Seung-Hoi | - |
dc.contributor.author | Choi, Hueng-Sik | - |
dc.date.accessioned | 2021-09-02T07:36:42Z | - |
dc.date.available | 2021-09-02T07:36:42Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-08-24 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/73729 | - |
dc.description.abstract | Under fasting conditions, activation of several hepatic genes sets the stage for gluconeogenesis in the liver. cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 2 (CRTC2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) are essential for this transcriptional induction of gluconeogenic genes. PGC-1insight that may help inform potential therapeutic approaches targeting PGC-l alpha-mediated regulation of hepatic glucose metabolism. induction is mediated by activation of a CREB/CRTC2 signaling complex, and recent findings have revealed that small heterodimer partner-interacting leucine zipper protein (SMILE), a member of the CREB/ATF family of basic region-leucine zipper (bZIP) transcription factors, is an insulin-inducible corepressor that decreases PGC-1 alpha expression and abrogates its stimulatory effect on hepatic gluconeogenesis. However, the molecular mechanism whereby SMILE suppresses PGC-1a expression is unknown. Here, we investigated SMII.E's effects on the CREB/CRTC2 signaling pathway and glucose metabolism. We found that SMILE significantly inhibits CREB/ CRTC2-induced PGC-1 alpha expression by interacting with and disrupting the CREB/CRTC2 complex. Consequently, SMILE decreased PGC-1 alpha-induced hepatic gluconeogenic gene expression. Furthermore, SMILE inhibited CREB/CRTC2-induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene expression by directly repressing the expression of these genes and by indirectly inhibiting the expression of PGC-1 alpha via CREB/CRTC2 repression. Indeed, enhanced gluconeogenesis and circulating blood glucose levels in mice injected with an adenovirus construct containing a constitutively active CRTC2 variant (CRTC2-S171A) were significantly reduced by WT SMILE, but not by leucine zipper-mutated SMILE. These results reveal that SMILE represses CREB/CRTC2-induced PGC-1 alpha expression, an insight that may help inform potential therapeutic approaches targeting PGC-1 alpha-mediated regulation of hepatic glucose metabolism. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | CREB COACTIVATOR CRTC2 | - |
dc.subject | HEPATIC GLUCONEOGENESIS | - |
dc.subject | HETERODIMER PARTNER | - |
dc.subject | KEY REGULATOR | - |
dc.subject | TORC2 | - |
dc.subject | PGC-1 | - |
dc.subject | DISRUPTION | - |
dc.subject | ZHANGFEI | - |
dc.subject | REGION | - |
dc.subject | LIVER | - |
dc.title | The SMILE transcriptional corepressor inhibits cAMP response element-binding protein (CREB)-mediated transactivation of gluconeogenic genes | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Han, Hye-Sook | - |
dc.contributor.affiliatedAuthor | Koo, Seung-Hoi | - |
dc.identifier.doi | 10.1074/jbc.RA118.002196 | - |
dc.identifier.scopusid | 2-s2.0-85052128454 | - |
dc.identifier.wosid | 000442730200013 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.293, no.34, pp.13125 - 13133 | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.title | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.volume | 293 | - |
dc.citation.number | 34 | - |
dc.citation.startPage | 13125 | - |
dc.citation.endPage | 13133 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | CREB COACTIVATOR CRTC2 | - |
dc.subject.keywordPlus | HEPATIC GLUCONEOGENESIS | - |
dc.subject.keywordPlus | HETERODIMER PARTNER | - |
dc.subject.keywordPlus | KEY REGULATOR | - |
dc.subject.keywordPlus | TORC2 | - |
dc.subject.keywordPlus | PGC-1 | - |
dc.subject.keywordPlus | DISRUPTION | - |
dc.subject.keywordPlus | ZHANGFEI | - |
dc.subject.keywordPlus | REGION | - |
dc.subject.keywordPlus | LIVER | - |
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