p53 protein is activated during muscle differentiation and participates with MyoD in the transcription of muscle creatine kinase gene

Abstract

The p53 protein is a transcription factor involved in processes of cell growth and di erentiation. The muscle creatine kinase (MCK) gene whose transcription is induced during muscle di erentiation contains p53-binding sites. In this study we tested the involvement of p53 in the activation of MCK transcription during muscle di erentiation of C2 cells. We have shown that the p53 protein is stabilized and its DNA binding and transcriptional activities are induced during muscle di erentiation. At the stage of muscle-di erentiation, p53 protein can induce the accurate transcription of a minimal p53-dependent MCK reporter gene. Moreover, p53 cooperates with MyoD in the induction of MCK transcription. The expression of a dominant negative p53 protein in muscle cells reduced the expression of endogenous MCK gene. The dominant negative p53 protein abolished the cooperativity of wild type p53 with MyoD. Amino and carboxy terminal residues of MyoD required for the cooperation with p53 in transcription were identi®ed. The cooperativity between the two proteins occurs also at the stage of DNA binding. We suggest that p53 protein is activated during myoblast di erentiation and participates with MyoD in the induction of MCK transcription.

Terminally Differentiated Human Neurons Repair Transcribed Genes but Display Attenuated Global DNA Repair and Modulation of Repair Gene Expression

“…A feedback mechanism, such as the known mdm2/p53 feedback loop (1), could be responsible for the subsequent transcriptional repression of p53. In fact, such a situation has been observed in several other terminally differentiated cell types such as myocytes and keratinocytes (20,26,32), in which p53 mRNA and, sometimes, protein levels are lower but the p53 activity is higher than that in precursor cells. Thus, it appears that p53 is generally activated posttranscriptionally upon differentiation.…”

p53 is involved in the differentiation but not in the differentiation-associated apoptosis of myoblasts

“…It has been found that during C2C12 differentiation p53 shows a transient increment of stability, measurable by pulse-chase experiments, 6 and a transient surge of transcriptional activity. 5 However, we could never couple this p53 transient stability and activation with a p53-positive immunofluorescence staining (S Soddu, unpublished results).…”

“…C2C12 myoblasts express wild-type p53 (wtp53) protein, which is activated during differentiation. 5,6 The interference with the endogenous wt-p53, by the expression of a dominantnegative p53 (dn-p53) protein, strongly inhibited terminal differentiation. 5 First, we investigated whether differentiation-associated apoptosis (DAA) and differentiation are mutually exclusive pathways, and therefore if there is the absence of simultaneous expression, in the same cell, of apoptosis and differentiation markers.…”

Muscle gets stressed? p53 represses and protects

“…10 In this issue, Yang et al propose a role of p53 in the activation of the myogenic differentiation checkpoint that relies on direct repression of myogenin-a MyoD downstream target gene, whose activation is required for myoblast progression toward terminal differentiation into multinucleated myotubes. 11,12 This finding is of particular interest, when considering that in unperturbed myoblasts p53 rather seems to contribute to muscle differentiation, 13,14 as it suggests that in myoblasts the activity of p53 is biased toward inhibiting differentiation by the DNA damage signaling. The authors first discovered the transcriptional repression of myogenin by p53 in the human rhabdomyosarcoma RD cell line.…”