Regulación de las proteínas 14-3-3 por acetilación. Estudio comparativo durante el ciclo celular y la diferenciación de células madre mesenquimales adultas
The 14-3-3 protein family constitutes an essential component in the regulation of the signaling machinery by coupling phosphorylated proteins in Ser/Thr residues. Considered redundant, ubiquitous and with relatively low variable levels, they have been studied as an accessory in several signaling pat...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2020
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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_6401 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6401.dir/6401.PDF |
| Aporte de: |
| Sumario: | The 14-3-3 protein family constitutes an essential component in the regulation of the signaling machinery by coupling phosphorylated proteins in Ser/Thr residues. Considered redundant, ubiquitous and with relatively low variable levels, they have been studied as an accessory in several signaling pathways. In this thesis, we evaluate the dynamics of inhibition by acetylation of its essential residue N-?-lysine 49/51 during the osteogenic differentiation process of hu-man mesenchymal stem cells derived from adipose tissue and the cell cycle. Firstly, we meas-ured the protein levels of the different family paralogs during osteogenesis and found an in-crease in the levels of the ? and ? paralogs, while ? was diminished. Likewise, we observed an increase in the absolute levels of 14-3-3AcK49/51 during the differentiation of the hASC and the S phase of the cell cycle. Among the seven family paralogs, inhibition by this MPT occurs mainly in the ? paralog and was observed as nuclear speckles. Silencing by shRNA of 14-3-3?, but not 14-3-3?, showed a significant increase in the transdifferentiation potential of 3T3-L1 preadipocytes. These results show that specifically 14-3-3? acts as a negative regulator of os-teogenesis and its inhibition by acetylation in K51 is one of the possible cellular mechanisms to bypass it. |
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