Felley-Bosco E, Weston A, Cawley H M, Bennett W P, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
Am J Hum Genet. 1993 Sep;53(3):752-9.
A rare germ-line polymorphism in codon 47 of the p53 gene replaces the wild-type proline (CCG) with a serine (TCG). Restriction analysis of 101 human samples revealed the frequency of the rare allele to be 0% (n = 69) in Caucasians and 4.7% (3/64, n = 32) among African-Americans. To investigate the consequence of this amino acid substitution, a cDNA construct (p53 mut47ser) containing the mutation was introduced into a lung adenocarcinoma cell line (Calu-6) that does not express p53. A growth suppression similar to that obtained after introduction of a wild-type p53 cDNA construct was observed, in contrast to the result obtained by introduction of p53 mut143ala. Furthermore, expression of neither p53 mut47ser nor wild-type p53 was tolerated by growing cells. In transient expression assays, both mut47ser and wild-type p53 activated the expression of a reporter gene linked to a p53 binding sequence (PG13-CAT) and inhibited the expression of the luciferase gene under the control of the Rous sarcoma virus promoter (RSVluc). In the same assay, mut143ala did not activate the expression of PG13-CAT and produced only a slight inhibitory effect on RSVluc. These findings indicate that the p53 variant with a serine at codon 47 should be considered as a rare germ-line polymorphism that does not alter the growth-suppression activity of p53.
p53基因第47密码子处一种罕见的种系多态性，将野生型脯氨酸（CCG）替换为丝氨酸（TCG）。对101份人类样本进行的限制性分析显示，在白种人中该罕见等位基因的频率为0%（n = 69），在非裔美国人中为4.7%（3/64，n = 32）。为了研究这种氨基酸替代的后果，将含有该突变的cDNA构建体（p53 mut47ser）导入不表达p53的肺腺癌细胞系（Calu-6）中。观察到其生长抑制作用与导入野生型p53 cDNA构建体后相似，这与导入p53 mut143ala的结果相反。此外，生长中的细胞既不能耐受p53 mut47ser的表达，也不能耐受野生型p53的表达。在瞬时表达试验中，mut47ser和野生型p53均激活了与p53结合序列（PG13-CAT）相连的报告基因的表达，并抑制了劳斯肉瘤病毒启动子（RSVluc）控制下的荧光素酶基因的表达。在相同试验中，mut143ala未激活PG13-CAT的表达，对RSVluc仅产生轻微抑制作用。这些发现表明，第47密码子处为丝氨酸的p53变体应被视为一种罕见的种系多态性，其不会改变p53的生长抑制活性。
