Molchadsky Alina, Shats Igor, Goldfinger Naomi, Pevsner-Fischer Meirav, Olson Melissa, Rinon Ariel, Tzahor Eldad, Lozano Guillermina, Zipori Dov, Sarig Rachel, Rotter Varda
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
PLoS One. 2008;3(11):e3707. doi: 10.1371/journal.pone.0003707. Epub 2008 Nov 12.
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.
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 mesenchymal cell types. In contrast, p53 is essential for skeletal muscle differentiation and osteogenic re-programming of skeletal muscle committed cells.
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.
肿瘤抑制因子p53是一种重要的调节因子，可控制包括细胞分化在内的各种细胞网络。有趣的是，一些研究表明p53促进细胞分化，而另一些研究则称其抑制分化。因此，评估这种不一致是否代表在各种分化程序中表现出的真实差异p53活性至关重要。
方法/主要发现：为了阐明这一重要问题，我们对几种间充质分化程序进行了比较研究。在代表几种分化程序不同阶段的小鼠和人间充质细胞中分析了p53敲低或活性增强的影响。我们发现p53下调主要分化诱导转录因子的表达，从而抑制多种间充质细胞类型的成骨、成脂和平滑肌分化。相反，p53对于骨骼肌分化和骨骼肌定向细胞的成骨重编程至关重要。
这些比较研究表明，根据特定的细胞类型和特定的分化程序，p53可能发挥正面或负面作用，因此总体上可被称为“分化守护者”。
