p53 plays a role in mesenchymal differentiation programs, in a cell fate dependent manner.
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.
Molchadsky
Alina
A
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shats
Igor
I
Goldfinger
Naomi
N
Pevsner-Fischer
Meirav
M
Olson
Melissa
M
Rinon
Ariel
A
Tzahor
Eldad
E
Lozano
Guillermina
G
Zipori
Dov
D
Sarig
Rachel
R
Rotter
Varda
V
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
D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D000099251:Myocardin