p53-independent apoptosis induced by muscle differentiation stimuli in polyomavirus large T-expressing myoblasts.
Abnormal proliferation signals, driven by cellular or viral oncogenes, can result in the induction of apoptosis under sub-optimal cell growth conditions. The tumor suppressor p53 plays a central role in mediating oncogene-induced apoptosis, therefore transformed cells lacking p53 are generally resistant to apoptosis-promoting treatments. In a previous work we have reported that the expression of polyomavirus large T antigen causes apoptosis in differentiating myoblasts and that this phenomenon is dependent on the onset of muscle differentiation in the absence of a correct cell cycle arrest. Here we report that polyomavirus large T increases the levels and activity of p53, but these alterations are not involved in the apoptotic mechanism. Apoptosis in polyomavirus large T-expressing myoblasts is not prevented by the expression of a p53 dominant-negative mutant nor it is increased by p53 over-expression. Moreover, forced differentiation induced through the over-expression of the muscle regulatory factor MyoD, leads to apoptosis without altering p53 function and, more significantly, even in a p53-null background. Our results indicate that apoptosis induced by the activation of muscle differentiation pathways in oncogene-expressing cells can occur in a p53-independent manner.
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Isituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma La Sapienza, Viale Regina Elena 324, Italy.
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D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells; D015870:Gene Expression; D016158:Genes, p53; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000166:cytology* / Q000821:virology*; D009154:Mutation; D017570:MyoD Protein / Q000235:genetics / Q000502:physiology; D009857:Oncogenes; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
D000952:Antigens, Polyomavirus Transforming; D017570:MyoD Protein; D016159:Tumor Suppressor Protein p53