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© The Rockefeller University Press,
0021-9525/2000//1295 $5.00
The Journal of Cell Biology, Volume 151, Number 6,
, 2000 1295-1304
Original Article |
P53 Regulates Myogenesis by Triggering the Differentiation Activity of Prb
soddu{at}ifo.it
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.
Key Words: p53 • Rb • MyoD • differentiation • muscle
© 2000 The Rockefeller University Press
Drs. Porrello, Cerone, and Coen contributed equally to the work and should be considered co-first authors.Dr. Cerone's present address is Department of Pathology and Molecular Medicine, McMaster University Medical Center, Hamilton, Ontario, Canada L8N 3Z5.
Dr. Coen's present address is Lautemberg Center for General and Tumor Immunology, Hebrew University-Hadassa Medical School, Jerusalem, Israel 91120.
Dr. Cimino's present address is Laboratory of Genetic Expression, University of Rome La Sapienza, 00153 Rome, Italy.
Abbreviations used in this paper: Act D, actinomycin D; DM, differentiation-promoting medium; dnp53, dominant-negative p53; GM, growth medium; MCK, muscle creatine kinase; MSC, mouse satellite cell; MyHC, myosin heavy chain.
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