title: p53 plays a role in mesenchymal differentiation programs, in a cell fate dependent manner.
abstract: BACKGROUND
  The tumor suppressor p53 is an important regulator that controls 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.
  
  
  RESULTS
  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 mesenchymal 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.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Molchadsky
authors.forename: Igor
authors.initials: I
authors.lastname: Shats
authors.forename: Naomi
authors.initials: N
authors.lastname: Goldfinger
authors.forename: Meirav
authors.initials: M
authors.lastname: Pevsner-Fischer
authors.forename: Melissa
authors.initials: M
authors.lastname: Olson
authors.forename: Ariel
authors.initials: A
authors.lastname: Rinon
authors.forename: Eldad
authors.initials: E
authors.lastname: Tzahor
authors.forename: Guillermina
authors.initials: G
authors.lastname: Lozano
authors.forename: Dov
authors.initials: D
authors.lastname: Zipori
authors.forename: Rachel
authors.initials: R
authors.lastname: Sarig
authors.forename: Varda
authors.initials: V
authors.lastname: Rotter
mesh_terms: D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099251:Myocardin
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D000099251:Myocardin