Chen Y, Chen P L, Lee W H
Center for Molecular Medicine, University of Texas Health Science Center at San Antonio 78245.
Mol Cell Biol. 1994 Oct;14(10):6764-72. doi: 10.1128/mcb.14.10.6764-6772.1994.
Inactivation of both alleles of the p53 gene is commonly found in human cancers. In contrast to mutations of the retinoblastoma gene, certain altered forms of p53 gain growth-promoting functions. To explore the mechanisms underlying this gain of function, we have identified two nuclear proteins, with molecular masses of 42 and 38 kDa, respectively, that are specifically associated with p53 mutated within the simian virus 40 T-antigen-binding domain, "hot spots" found in many human tumors. These mutants transactivate the multiple-drug resistance gene promoter and cause cells to grow to higher density. Both the mutated p53 complex with p42 and p38 increase when cells enter S phase of the cell cycle but decrease in G1 and M phases, suggesting that they may have a role in promoting cell growth.
p53基因的两个等位基因失活在人类癌症中很常见。与视网膜母细胞瘤基因的突变不同，某些p53的改变形式具有促进生长的功能。为了探究这种功能获得的潜在机制，我们鉴定出了两种核蛋白，其分子量分别为42 kDa和38 kDa，它们与在猿猴病毒40 T抗原结合域内发生突变的p53特异性相关，该结合域是在许多人类肿瘤中发现的“热点”。这些突变体可激活多药耐药基因启动子并使细胞生长至更高密度。当细胞进入细胞周期的S期时，与p42和p38形成的突变p53复合物均增加，但在G1期和M期减少，这表明它们可能在促进细胞生长中发挥作用。
