The P73 gene is transcribed from two promoters, P1 and P2, that direct the expression of multiple transactivation competent (TA) and dominant negative (DN) isoforms. TAp73 transcription factors mediate cell cycle arrest and/or apoptosis in response to DNA damage and are involved in developmental processes. P73 mRNA levels increase and the P1p73 promoter is upregulated during myogenic differentiation of C2C12 skeletal muscle satellite cells. The DNp73 proteins act as trans-repressors of p53- and p73-dependent transcription, and possess both antiapoptotic and pro-proliferative potential. Here, we show that DNp73 alpha is expressed in proliferating C2C12 myoblasts, rapidly accumulates in differentiating myocytes and remains elevated in C2C12 myotubes. By combining transactivation assays and chromatin immunoprecipitation analysis, we could show that the upregulation of the P2p73 promoter during myogenic differentiation is mediated by the coordinated recruitment and activity of MyoD and p53/p73. Abrogation of DNp73 expression by specific siRNA led to a strong potentiation of the spontaneous apoptosis of C2C12 myoblasts induced to differentiate. Finally, unlike TAp73 that contributes to DNA damage-induced apoptosis of myotubes, endogenous DNp73 mediates the relative resistance of differentiated myotubes to DNA damage. Altogether, our findings identify DNp73 alpha as an important target in designing strategies aimed at the potentiation of the regenerative potential of skeletal satellite cells.

Belloni, L., Moretti, F., Merlo, P., Damalas, A., Costanzo, A., Blandino, G., et al. (2006). DNp73 alpha protects myogenic cells from apoptosis. ONCOGENE, 25(25), 3606-3612 [10.1038/sj.onc.1209321].

DNp73 alpha protects myogenic cells from apoptosis

COSTANZO, ANTONIO;
2006-01-01

Abstract

The P73 gene is transcribed from two promoters, P1 and P2, that direct the expression of multiple transactivation competent (TA) and dominant negative (DN) isoforms. TAp73 transcription factors mediate cell cycle arrest and/or apoptosis in response to DNA damage and are involved in developmental processes. P73 mRNA levels increase and the P1p73 promoter is upregulated during myogenic differentiation of C2C12 skeletal muscle satellite cells. The DNp73 proteins act as trans-repressors of p53- and p73-dependent transcription, and possess both antiapoptotic and pro-proliferative potential. Here, we show that DNp73 alpha is expressed in proliferating C2C12 myoblasts, rapidly accumulates in differentiating myocytes and remains elevated in C2C12 myotubes. By combining transactivation assays and chromatin immunoprecipitation analysis, we could show that the upregulation of the P2p73 promoter during myogenic differentiation is mediated by the coordinated recruitment and activity of MyoD and p53/p73. Abrogation of DNp73 expression by specific siRNA led to a strong potentiation of the spontaneous apoptosis of C2C12 myoblasts induced to differentiate. Finally, unlike TAp73 that contributes to DNA damage-induced apoptosis of myotubes, endogenous DNp73 mediates the relative resistance of differentiated myotubes to DNA damage. Altogether, our findings identify DNp73 alpha as an important target in designing strategies aimed at the potentiation of the regenerative potential of skeletal satellite cells.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/35 - Malattie Cutanee e Veneree
English
Con Impact Factor ISI
p73; DNp73; myogenic differentiation; apoptosis
Belloni, L., Moretti, F., Merlo, P., Damalas, A., Costanzo, A., Blandino, G., et al. (2006). DNp73 alpha protects myogenic cells from apoptosis. ONCOGENE, 25(25), 3606-3612 [10.1038/sj.onc.1209321].
Belloni, L; Moretti, F; Merlo, P; Damalas, A; Costanzo, A; Blandino, G; Levrero, M
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34278
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