p53 regulates myogenesis by triggering the differentiation activity of pRb

Alessandro Porrello, Maria Antonietta Cerone, Sabrina Coen, Aymone Gurtner, Giulia Fontemaggi, Letizia Cimino, Giulia Piaggio, Ada Sacchi, Silvia Soddu

Research output: Contribution to journalArticle

Abstract

The p53 oncosuppressor protein regulates cell cycle checkpoints and apoptosis, but increasing evidence also indicates its involvement in differentiation and development. We had previously demonstrated that in the presence of differentiation-promoting stimuli, p53-defective myoblasts exit from the cell cycle but do not differentiate into myocytes and myotubes. To identify the pathways through which p53 contributes to skeletal muscle differentiation, we have analyzed the expression of a series of genes regulated during myogenesis in parental and dominant-negative p53 (dnp53)-expressing C2C12 myoblasts. We found that in dnp53-expressing C2C12 cells, as well as in p53(-/-) primary myoblasts, pRb is hypophosphorylated and proliferation stops. However, these cells do not upregulate pRb and have reduced MyoD activity. The transduction of exogenous TP53 or Rb genes in p53-defective myoblasts rescues MyoD activity and differentiation potential. Additionally, in vivo studies on the Rb promoter demonstrate that p53 regulates the Rb gene expression at transcriptional level through a p53-binding site. Therefore, here we show that p53 regulates myoblast differentiation by means of pRb without affecting its cell cycle-related functions.

Original languageEnglish
Pages (from-to)1295-1303
Number of pages9
JournalJournal of Cell Biology
Volume151
Issue number6
DOIs
Publication statusPublished - Dec 11 2000

Fingerprint

Muscle Development
Myoblasts
Retinoblastoma Genes
Cell Cycle
p53 Genes
Skeletal Muscle Fibers
Cell Cycle Checkpoints
Muscle Cells
Skeletal Muscle
Up-Regulation
Binding Sites
Apoptosis
Gene Expression
Genes
Proteins

Keywords

  • Differentiation
  • Muscle
  • MyoD
  • p53
  • Rb

ASJC Scopus subject areas

  • Cell Biology

Cite this

p53 regulates myogenesis by triggering the differentiation activity of pRb. / Porrello, Alessandro; Cerone, Maria Antonietta; Coen, Sabrina; Gurtner, Aymone; Fontemaggi, Giulia; Cimino, Letizia; Piaggio, Giulia; Sacchi, Ada; Soddu, Silvia.

In: Journal of Cell Biology, Vol. 151, No. 6, 11.12.2000, p. 1295-1303.

Research output: Contribution to journalArticle

Porrello, A, Cerone, MA, Coen, S, Gurtner, A, Fontemaggi, G, Cimino, L, Piaggio, G, Sacchi, A & Soddu, S 2000, 'p53 regulates myogenesis by triggering the differentiation activity of pRb', Journal of Cell Biology, vol. 151, no. 6, pp. 1295-1303. https://doi.org/10.1083/jcb.151.6.1295
Porrello A, Cerone MA, Coen S, Gurtner A, Fontemaggi G, Cimino L et al. p53 regulates myogenesis by triggering the differentiation activity of pRb. Journal of Cell Biology. 2000 Dec 11;151(6):1295-1303. https://doi.org/10.1083/jcb.151.6.1295
Porrello, Alessandro ; Cerone, Maria Antonietta ; Coen, Sabrina ; Gurtner, Aymone ; Fontemaggi, Giulia ; Cimino, Letizia ; Piaggio, Giulia ; Sacchi, Ada ; Soddu, Silvia. / p53 regulates myogenesis by triggering the differentiation activity of pRb. In: Journal of Cell Biology. 2000 ; Vol. 151, No. 6. pp. 1295-1303.
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