VTechWorks staff will be away for the winter holidays starting Tuesday, December 24, 2024, through Wednesday, January 1, 2025, and will not be replying to requests during this time. Thank you for your patience, and happy holidays!
 

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

Simple item page
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

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
me%2E2008-0010.pdf
Size:
360.94 KB
Format:
Adobe Portable Document Format
Description:
Main article
Download

Collections

Scholarly Works, Human Nutrition, Foods, and Exercise