Reversible proline-directedphosphorylation at Ser/Thr-Pro motifs has anessential role in myogenesis, a multistep processstrictly regulated by several signalling pathwaysthat impinge on two families of myogeniceffectors, the basic Helix Loop Helix (bHLH)myogenic transcription factors and the MyocyteEnhancer Factor 2 (MEF2) proteins. Thequestion of how these signals are deciphered bythe myogenic effectors remains largelyundefined. In this study we show that thepeptidyl-prolyl isomerase Pin1, which catalyzesthe isomerization of phosphorylated Ser/Thr-Propeptide bonds to induce conformational changesof its target proteins, acts as an inhibitor ofmuscle differentiation as its knock-down inmyoblasts promotes myotube formation. Withthe aim of clarifying the mechanism of Pin1function in skeletal myogenesis, we investigatedwhether MEF2C, a critical regulator of themyogenic program that is the endpoint of severalsignalling pathways, might serve as a/the targetfor the inhibitory effects of Pin1 on muscledifferentiation. We show that Pin1 interactsselectively with phosphorylated MEF2C inskeletal muscle cells, both in vitro and in vivo.The interaction with Pin1 requires two novelcritical pSer/Thr-Pro motifs in MEF2C, Ser98and Ser110, which are phosphorylated in vivo.Overexpression of Pin1 decreases MEF2Cstability and activity, and its ability to cooperatewith MyoD to activate myogenic conversion.Collectively these findings reveal a novel role forPin1 as a regulator of muscle terminaldifferentiation and suggest that Pin1 mediatedrepression of MEF2C function could contributeto this function.
PROLINE ISOMERASE PIN1 REPRESSES TERMINAL DIFFERENTIATION AND MYOCYTEENHANCER FACTOR 2C FUNCTION IN SKELETAL MUSCLE CELLS / Magli, Alessandro; Angelelli, Cecilia; Ganassi, Massimo; Baruffaldi, Fiorenza; V., Matafora; Battini, Renata; A., Bachi; G., Messina; A., Rustighi; G., Del Sal; S., Ferrari; Molinari, Susanna. - In: JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 1083-351X. - STAMPA. - 285(2010), pp. 34518-34527.
Data di pubblicazione: | 2010 |
Titolo: | PROLINE ISOMERASE PIN1 REPRESSES TERMINAL DIFFERENTIATION AND MYOCYTEENHANCER FACTOR 2C FUNCTION IN SKELETAL MUSCLE CELLS |
Autore/i: | Magli, Alessandro; Angelelli, Cecilia; Ganassi, Massimo; Baruffaldi, Fiorenza; V., Matafora; Battini, Renata; A., Bachi; G., Messina; A., Rustighi; G., Del Sal; S., Ferrari; Molinari, Susanna |
Autore/i UNIMORE: | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1074/jbc.M110.104133 |
Rivista: | |
Volume: | 285 |
Pagina iniziale: | 34518 |
Pagina finale: | 34527 |
Codice identificativo Scopus: | 2-s2.0-78049397634 |
Codice identificativo Pubmed: | 20801874 |
Citazione: | PROLINE ISOMERASE PIN1 REPRESSES TERMINAL DIFFERENTIATION AND MYOCYTEENHANCER FACTOR 2C FUNCTION IN SKELETAL MUSCLE CELLS / Magli, Alessandro; Angelelli, Cecilia; Ganassi, Massimo; Baruffaldi, Fiorenza; V., Matafora; Battini, Renata; A., Bachi; G., Messina; A., Rustighi; G., Del Sal; S., Ferrari; Molinari, Susanna. - In: JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 1083-351X. - STAMPA. - 285(2010), pp. 34518-34527. |
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