Estudio de la especificidad de la familia de proteínas 14-3-3 en la regulación de TAZ en células madre mesenquimales adultas

MSCs (mesenchymal stem cells) can differentiate to adipocytes and osteoblasts, among other\nmesenchymal cells. Upon activation of the Hippo pathway, the transcriptional co-regulator\nTAZ, is phosphorylated in its Ser 89, which causes its binding to 14-3-3 regulatory proteins\nin the cytoplasm. This...

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Autor principal: Gojanovich, Aldana Daniela
Otros Autores: Uhart, Marina
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2017
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1422
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1422.dir/1422.PDF
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Sumario:MSCs (mesenchymal stem cells) can differentiate to adipocytes and osteoblasts, among other\nmesenchymal cells. Upon activation of the Hippo pathway, the transcriptional co-regulator\nTAZ, is phosphorylated in its Ser 89, which causes its binding to 14-3-3 regulatory proteins\nin the cytoplasm. This prevents the repression of adipogenesis involved genes. In mammals,\nthe 14-3-3 family is composed of 7 paralogs that specifically bind serine or threonine\nphosphorylated residues (pS / T) in their target proteins. Our hypothesis was that the\ninteraction with TAZ was specific to one or a few 14-3-3 paralogs. Variations of the levels of these paralogs were observed during the adipogenesis of hASCs and 3T3-L1 cells. The\nvariation occurred both at mRNA and protein level, being specific for the paralogs 14-3-3y,\nB, n and E. The paralog that showed the greatest variation was 14-3-3y, wich values increased\nduring the adipogenesis of both hASCs and 3T3-L1. The results after silencing 14-3-3B\nsuggestes that this paralog could regulate the subcellular localization of TAZ. Our analysis\nsupports the current concept of specific molecular functions for the different paralogs of 14-\n3-3.