Harms K, Nozell S, Chen X
Department of Cell Biology, University of Alabama at Birmingham, 1918 University Blvd., Birmingham, Alabama 35294, USA.
Cell Mol Life Sci. 2004 Apr;61(7-8):822-42. doi: 10.1007/s00018-003-3304-4.
p53 is the most commonly mutated gene in human cancer. After activation by cellular stresses such as DNA damage or oncogene activation, p53, a sequence-specific DNA-binding protein, induces the expression of target genes which mediate tumor suppression. Two recently identified p53 homologues, p63 and p73, appear to function similarly to p53, that is, they both activate target gene expression and suppress cell growth when overexpressed; however, the p63 and p73 genes are rarely mutated in human cancer and do not adhere to Knudson's classical model of a tumor suppressor gene. Recently, exciting observations suggest nonoverlapping functions for the family members. Herein, we outline the recent literatures identifying and characterizing both the common and distinct target genes of the p53 family transcription factors in relation to their signaling pathways.
p53是人类癌症中最常发生突变的基因。在受到诸如DNA损伤或癌基因激活等细胞应激激活后，p53作为一种序列特异性DNA结合蛋白，会诱导介导肿瘤抑制的靶基因表达。最近鉴定出的两个p53同源物p63和p73，似乎与p53功能相似，也就是说，它们在过表达时都会激活靶基因表达并抑制细胞生长；然而，p63和p73基因在人类癌症中很少发生突变，并不符合Knudson经典的肿瘤抑制基因模型。最近，令人兴奋的观察结果表明该家族成员具有非重叠功能。在此，我们概述了近期有关鉴定和表征p53家族转录因子的共同及独特靶基因及其信号通路的文献。
