P53 plays a role in mesenchymal differentiation programs, in a cell fate dependent manner

Alina Molchadsky, Igor Shats, Naomi Goldfinger, Meirav Pevsner-Fischer, Melissa Olson, Ariel Rinon, Eldad Tzahor, Guillermina Lozano, Dov Zipori, Rachel Sarig, Varda Rotter

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The tumor suppressor p53 is an important regulator that control various cellular networks, including cell differentiation. Interestingly, some studies suggest that p53 facilitates cell differentiation, whereas others claim that it suppresses differentiation. Therefore, it is critical to evaluate whether this inconsistency represents an authentic differential p53 activity manifested in the various differentiation programs. Methodology/Principal Findings: To clarify this important issue, we conducted a comparative study of several mesenchymal differentiation programs. The effects of p53 knockdown or enhanced activity were analyzed in mouse and human mesenchymal cells, representing various stages of several differentiation programs. We found that p53 down-regulated the expression of master differentiation-inducing transcription factors, thereby inhibiting osteogenic, adipogenic and smooth muscle differentiation of multiple mesenchymall cell types. In contrast, p53 is essential for skeletal muscle differentiation and osteogenic re-programming of skeletal muscle committed cells. Conclusions: These comparative studies suggest that, depending on the specific cell type and the specific differentiation program p53 may exert a positive or a negative effect, and thus can be referred as a "guardian of differentiation" at large.

Original languageEnglish (US)
Article numbere3707
JournalPloS one
Volume3
Issue number11
DOIs
StatePublished - Nov 12 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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