P53参与抑制PC-1基因转录的结构域分析  

Analysis of Functional Domains of P53 Participated in Repression of PC-1 Transcription

作　　者：王健[1] 张惠[1] 周建光[1] 

机构地区：[1]军事医学科学院生物工程研究所,北京100850

出　　处：《生物技术通讯》2007年第3期371-373,共3页Letters in Biotechnology

基　　金：国家自然科学基金项目(30070296)

摘　　要：目的:分析P53分子参与抑制PC-1基因转录的结构域。方法:构建P53分子突变体;将前列腺癌LNCaP细胞瞬时转染野生型或突变型p53及含PC-1启动子的荧光素酶表达载体p4939,分析PC-1启动子的转录活性。结果:P53分子N端转录激活域及富含脯氨酸功能域突变体没有减弱对PC-1启动子的转录抑制作用,而特异性DNA结合域上175、273位突变体和C端339～346位氨基酸的缺失突变体都减弱了对PC-1启动子转录的抑制作用;另外P53分子第175和273位突变体在前列腺癌细胞中对野生型P53的转录抑制功能表现出显性负效应。结论:P53分子特异性DNA结合域和C端结构域参与对PC-1基因启动子的转录抑制,而P53突变体的显性负效应可能是PC-1在前列腺癌进展中表达失调的因素之一。Objective： To analyze functional domains of P53 which are participated in repression of PC-1 transcription. Methods： The P53 mutants were constructed. Prostate cancer cell LNCaP was transiently transfected with expression vectors encoding mr-P53, wt-P53 and luciferase-vector p4939, and the PC-1 promoter activity was detected. Results： The N-terminus transactivation domain and proline-rich domain of P53 mutants did not attenuate the repression of PC-1 promoter activity, while the 175 and 273 site mutants in DNA-specific binding domain and C-terminal amino acids 339-346 deletion mutant of P53 all resulted in a loss of the repression of the PC-1 promoter activity. Moreover, 175 and 273 mutants of P53 both displayed the dominant negative effect over wt-P53 in the prostate cancer cells. Conclusion： These observations reveal that the DNA-specific binding domain and C-terminal domain are required for the P53 repression function on the PC-1 promoter and the dominant negative effect of P53 mutants may play a role in the dysregulation of PC-1 expression in the development of the prostate cancer.

关 键 词：PC-1 P53 抑制 功能域 

分 类 号：Q78[生物学—分子生物学]