Marcel V, Hainaut P
International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
Cell Mol Life Sci. 2009 Feb;66(3):391-406. doi: 10.1007/s00018-008-8336-3.
For 25 years, the p53 tumor suppressor protein was considered the only protein expressed by the (TP53) gene. However, in several studies the existence of p53 alternative transcripts in mouse and human cells has been documented, while their expression patterns and functions remained a mystery. Since 2002, several groups have identified and described the existence of up to 10 p53 isoforms and have demonstrated their roles in modulation of p53 suppressive activity. It is now clear that the patterns of p53 expression are much more complex than previously recognized and that these isoforms have the potential to act either synergistically or antagonistically, depending on their structure and mechanism of production. This review focuses on the different ways to produce p53 isoforms, on their specific properties, on their effect on p53 suppressive activity as well as on their implication in a new potential mechanism involved in p53 deregulation in cancer.
25年来,p53肿瘤抑制蛋白一直被认为是(TP53)基因表达的唯一蛋白质。然而,多项研究已证明小鼠和人类细胞中存在p53可变转录本,但其表达模式和功能仍是个谜。自2002年以来,多个研究小组已鉴定并描述了多达10种p53异构体的存在,并证明了它们在调节p53抑制活性中的作用。现在很清楚,p53的表达模式比以前认为的要复杂得多,而且这些异构体有可能根据其结构和产生机制协同或拮抗发挥作用。本综述重点关注产生p53异构体的不同方式、它们的特定特性、它们对p53抑制活性的影响以及它们在癌症中p53失调所涉及的新潜在机制中的作用。