Ruolo della fosfolipasi C-β1 nel differenziamento miogenico: identificazione di nuovi target nucleari

Ramazzotti, Giulia (2008) Ruolo della fosfolipasi C-β1 nel differenziamento miogenico: identificazione di nuovi target nucleari, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze morfologiche umane e molecolari, 20 Ciclo. DOI 10.6092/unibo/amsdottorato/1074.
Documenti full-text disponibili:
Documento PDF (Italiano) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (1MB) | Anteprima


The expression of phospholipase C-β1 (PLC-β1) and cyclin D3 is highly induced during skeletal myoblast differentiation. We have previously shown that PLC-β1 activates cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLC-β1 is a crucial regulator of mouse cyclin D3 gene. Here we report that PLC-β1 catalytic activity plays a role in the increase of cyclin D3 levels and in the induction of differentiation of C2C12 skeletal muscle cells. PLC-β1 mutational analysis revealed the importance of His331 and His378 for the catalytic activity. We show that following insulin administration, cyclin D3 mRNA levels are lower in cells overexpressing the PLC-β1 catalytically inactive form, as compared to wild type cells. We describe a novel signaling pathway elicited by PLC-β1 that modulates Activator Protein-1 (AP-1) activity. Indeed, gel mobility shift assays indicate that there is a c-jun binding site located in cyclin D3 promoter region specifically regulated by PLC-β1 and that c-jun binding activity is significantly increased by insulin stimulation and PLC-β1 overexpression. Moreover, mutation of c-jun/AP-1 binding site decreases the basal cyclin D3 promoter activity and eliminates its induction by insulin and PLC-β1 overexpression. Interestingly, we observed that the ectopic expression of the Inositol Polyphosphate Multikinase (IPMK) in C2C12 myoblasts enhances cyclin D3 gene expression and that the mutation of c-jun site in cyclin D3 promoter determines an impairment of IPMK-dependent promoter induction. These results indicate that PLC-β1 activates a c-jun/AP-1 target gene, i.e. cyclin D3, during myogenic differentiation through IPMK signaling.

Tipologia del documento
Tesi di dottorato
Ramazzotti, Giulia
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
differenziamento muscolare fosfolipasi c-β1 ciclina d3 c-jun ipmk nucleo
Data di discussione
26 Maggio 2008

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi