Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Carcinogenesis. 2010 Sep;31(9):1501-8. doi: 10.1093/carcin/bgq101. Epub 2010 May 26.
Many of the roles played by the tumor suppressor p53 in restraining cancer initiation and progression are well established. These include the ability of p53 to induce cell-cycle arrest, DNA repair, senescence and apoptosis. In addition, during the 30 years of p53 research, numerous studies have implicated p53 in the regulation of differentiation and developmental pathways. Here, we summarize the data on these relatively less-characterized functions of p53, including its involvement in embryogenesis and various differentiation programs, as well as its function in restraining de-differentiation of mature somatic cells. Besides the well-known functions of p53 as a cell-cycle regulator and a mediator of apoptosis, both coincide with differentiation processes, p53 was shown to exert its effects on various differentiation programs via direct regulation of specific key factors controlling these programs. The complex regulation by p53, which acts to suppress or to induce differentiation, is mainly the result of the specific cell type and fate. We argue that regulation of differentiation is pivotal for the tumor-suppressive activity of p53, which act to maintain the proper cellular state, preventing improper maturation or reprogramming. This conclusion is further supporting the notion that aberrant differentiation is associated with malignant transformation.
抑癌基因 p53 在抑制癌症发生和进展方面所扮演的许多角色已经得到充分证实。这些角色包括 p53 诱导细胞周期停滞、DNA 修复、衰老和凋亡的能力。此外，在 p53 研究的 30 年中，许多研究表明 p53 参与了分化和发育途径的调节。在这里，我们总结了关于 p53 这些相对较少被描述的功能的数据，包括它在胚胎发生和各种分化程序中的作用，以及它在抑制成熟体细胞去分化中的作用。除了众所周知的作为细胞周期调节剂和凋亡介体的功能外，p53 都与分化过程相吻合，p53 被证明通过直接调节控制这些程序的特定关键因子来发挥其对各种分化程序的作用。p53 的复杂调节作用，既可以抑制也可以诱导分化，主要是由于特定的细胞类型和命运。我们认为，分化的调节对于 p53 的肿瘤抑制活性至关重要，它可以维持适当的细胞状态，防止不当成熟或重新编程。这一结论进一步支持了异常分化与恶性转化相关的观点。
