Kubbutat M H, Vousden K H
ABL-Basic Research Program, Frederick Cancer Research and Developmental Center, National Cancer Institute, MD 21702, USA.
Mol Med Today. 1998 Jun;4(6):250-6. doi: 10.1016/s1357-4310(98)01260-x.
The tumor suppressor protein p53 plays a pivotal role in protection against the development of cancer and is inactivated in many human malignancies. p53 is thought to prevent accumulation of genomic alterations by hindering cell proliferation in response to genotoxic stress, and two of the principal functions of p53 are the induction of cell-cycle arrest and the activation of apoptotic cell death. Because p53 is an extremely efficient inhibitor of cell growth, keeping p53 function under control in normal cells is critical. One of the principal mechanisms by which cells achieve this is by regulating the p53 protein level, although the ability of the protein to adopt active and latent forms and its cellular localization also contribute to the regulation of its function. Here, we summarize recently identified mechanisms that regulate the stability of the p53 protein and discuss the potentially immense clinical relevance of these observations in developing therapeutical approaches that aim to restore p53 function in human tumors.
肿瘤抑制蛋白p53在预防癌症发生中起关键作用，且在许多人类恶性肿瘤中失活。p53被认为可通过在基因毒性应激反应中阻碍细胞增殖来防止基因组改变的积累，p53的两个主要功能是诱导细胞周期停滞和激活凋亡性细胞死亡。由于p53是一种极其有效的细胞生长抑制剂，在正常细胞中控制p53的功能至关重要。细胞实现这一点的主要机制之一是调节p53蛋白水平，尽管该蛋白形成活性和潜在形式的能力及其细胞定位也有助于其功能的调节。在此，我们总结了最近发现的调节p53蛋白稳定性的机制，并讨论了这些观察结果在开发旨在恢复人类肿瘤中p53功能的治疗方法方面潜在的巨大临床相关性。
