dc.creator | Nieto, Leandro Eduardo | |
dc.creator | Fuertes, Mariana | |
dc.creator | Rosmino, Josefina | |
dc.creator | Senin, Sergio Ariel | |
dc.creator | Arzt, Eduardo Simon | |
dc.date.accessioned | 2021-02-03T13:26:49Z | |
dc.date.accessioned | 2022-10-15T06:15:46Z | |
dc.date.available | 2021-02-03T13:26:49Z | |
dc.date.available | 2022-10-15T06:15:46Z | |
dc.date.created | 2021-02-03T13:26:49Z | |
dc.date.issued | 2019-10 | |
dc.identifier | Nieto, Leandro Eduardo; Fuertes, Mariana; Rosmino, Josefina; Senin, Sergio Ariel; Arzt, Eduardo Simon; Crosstalk of BMP-4 and RA signaling pathways on Pomc gene regulation in corticotrophs; BioScientifica; Journal of Molecular Endocrinology; 63; 3; 10-2019; 161-174 | |
dc.identifier | 0952-5041 | |
dc.identifier | http://hdl.handle.net/11336/124573 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4354186 | |
dc.description.abstract | Retinoic acid (RA), an active metabolite of Vitamin A, and bone morphogenetic protein 4 (BMP-4) pathways control the transcription of pro-opiomelanocortin (Pomc), the precursor of ACTH. We describe a novel mechanism by which RA and BMP-4 act together in the context of pituitary corticotroph tumoral cells to regulate Pomc transcription. BMP-4 and RA exert a potentiated inhibition on Pomc gene expression. This potentiation of the inhibitory action on Pomc transcription was blocked by the inhibitory SMADs of the BMP-4 pathway (SMAD6 and SMAD7), a negative regulator of BMP-4 signaling (TOB1) and a blocker of RA pathway (COUP-TFI). AtT-20 corticotrophinoma cells express RA receptors (RARB, RXRA and RXRG) which associate with factors of BMP-4 (SMAD4 and SMAD1) signaling cascade in transcriptional complexes that block Pomc transcription. COUP-TFI and TOB1 disrupt these complexes. Deletions and mutations of the Pomc promoter and a specific DNA-binding assay show that the complexes bind to the RARE site in the Pomc promoter. The enhanced inhibitory interaction between RA and BMP-4 pathways occurs also in another relevant corticotroph gene promoter, the corticotropin-releasing hormone receptor 1 (Crh-r1). The understanding of the molecules that participate in the control of corticotroph gene expression contribute to define more precise targets for the treatment of corticotrophinomas. | |
dc.language | eng | |
dc.publisher | BioScientifica | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://jme.bioscientifica.com/view/journals/jme/63/3/JME-19-0059.xml | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1530/JME-19-0059 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | BMP-4 | |
dc.subject | CORTICOTROPH | |
dc.subject | POMC | |
dc.subject | RETINOIC ACID | |
dc.subject | SMAD | |
dc.title | Crosstalk of BMP-4 and RA signaling pathways on Pomc gene regulation in corticotrophs | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |