Ruolo della regolazione post-traduzionale del fattore di trascrizione FoxO3 nel muscolo scheletrico durante l'atrofia muscolare
Year: 2011
Type: dissertation
Abstract: FoxO proteins are transcription factors that control cell cycle progression, DNA repair, muscle atrophy, stress resistance and apoptosis. These divergent functions are carefully regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination, these mechanisms seem to coordinate the localization, activity and longevity of FoxO protein in a time-dependent manner to ensure a fine regulation. During muscle atrophy FoxO3 is negatively regulated by AKT phosphorylation, which determines its nuclear localization and activation. We studied the role of acetylation on FoxO3 in adult skeletal muscle, a post translational modification that modulates FoxO activity. To fulfill this purpose, we have generated different FoxO3 mutants which prevent acetylation (KR) or mimic acetylation (KQ). By a Luciferase assay, we discovered that mutants show the opposite behavior in activating the promoter, notably acetylation-mimicking mutants displayed a lower transcriptional activity. Moreover hyperacetylation reduces FoxO-dependent muscle atrophy by causing re-localization of FoxO proteins into the cytoplasm. Finally we found out that along with the quantity of the acetylated residues their position is important as well. In particular K262 seems to be a key residue for the nuclear export. In conclusion, we can assert that our findings shed light on the complex regulation of FoxO transcription factors, explaining how acetylation negatively modulates FoxO activity.
Author: Enrico Bertaggia
Language: Italian
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W51055147