Nescient helix-loop-helix 2 interacts with signal transducer and activator of transcription 3 to regulate transcription of prohormone convertase 1/3

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dc.contributor.authorFox, D. L.en
dc.contributor.authorGood, Deborah J.en
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessed2014-07-07en
dc.date.accessioned2014-07-08T13:02:19Zen
dc.date.available2014-07-08T13:02:19Zen
dc.date.issued2008-06en
dc.description.abstractMechanisms controlling body weight involve gene regulation through the activation of signal transduction pathways. The Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway is the mechanism primarily used by leptin in the hypothalamus. The transcription factor nescient helix-loop-helix 2 (Nhlh2) is a downstream target of leptin signaling and is expressed in proopiomelanocortin arcuate neurons. Proopiomelanocortin is cleaved by prohormone convertase 1/3 (PC1/3) to produce peptides that regulate the body's response to energy availability. Previous studies show that the PC1/3 promoter contains STAT3 sites mediating leptin-induced PC1/3 expression, and that Nhlh2 is required for hypothalamic PC1/3 expression because Nhlh2 knockout mice have reduced PC1/3 mRNA levels. Studies herein reveal that leptin-induced PC1/3 gene expression is abrogated in N2KO mice, and that in a hypothalamic cell line both STAT3 and Nhlh2 are required for the full transcriptional response of a PC1/3 reporter gene after leptin stimulation. Furthermore, it is shown that Nhlh2 binds to E-box motifs found adjacent to STAT3 sites in the PC1/3 promoter both in vitro and in chromatin immunoprecipitation assays. Finally, two different protein-protein interaction assays confirm the presence of a STAT3: Nhlh2 heterodimer on the PC1/3 promoter. The Nhlh2: STAT3 heterodimer may be an important transcriptional regulator of other hypothalamic genes in the leptin signaling pathway. These data confirm Nhlh2 as an integral element of the Janus kinase/STAT signaling pathway and are the first to demonstrate coordinated control of PC1/3 transcription by Nhlh2 and STAT3 after leptin stimulation.en
dc.description.sponsorshipNIH Grant DK059903en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDana L. Fox, and Deborah J. Good. "Nescient Helix-Loop-Helix 2 Interacts with Signal Transducer and Activator of Transcription 3 to Regulate Transcription of Prohormone Convertase 1/3," Molecular Endocrinology 2008 22:6, 1438-1448. DOI: http://dx.doi.org/10.1210/me.2008-0010en
dc.identifier.doihttps://doi.org/10.1210/me.2008-0010en
dc.identifier.issn0888-8809en
dc.identifier.urihttp://hdl.handle.net/10919/49398en
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/me.2008-0010en
dc.language.isoenen
dc.publisherEndocrine Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectprothyrotropin-releasing hormoneen
dc.subjectgene-expressionen
dc.subjectprohormoneen
dc.subjectconvertase-1en
dc.subjectarcuate nucleusen
dc.subjectbody-weighten
dc.subjectob/ob miceen
dc.subjectleptinen
dc.subjectObesityen
dc.subjectnhlh2en
dc.subjectproopiomelanocortinen
dc.subjectendocrinology & metabolismen
dc.titleNescient helix-loop-helix 2 interacts with signal transducer and activator of transcription 3 to regulate transcription of prohormone convertase 1/3en
dc.title.serialMolecular Endocrinologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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