WILD-TYPE P53 MEDIATES POSITIVE REGULATION OF GENE-EXPRESSION THROUGH A SPECIFIC DNA-SEQUENCE ELEMENT
WILD-TYPE P53 MEDIATES POSITIVE REGULATION OF GENE-EXPRESSION THROUGH A SPECIFIC DNA-SEQUENCE ELEMENT
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DOI：
10.1101/gad.6.7.1143
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发表时间：
1992-07-01
影响因子：
10.5
通讯作者：
LEVINE, AJ
中科院分区：
文献类型：
--
作者：
ZAMBETTI, GP;BARGONETTI, J;LEVINE, AJ
最近有报道称，野生型p53基因产物可以正向调节与鼠肌肉特异性肌酸激酶（MCK）基因的增强子-启动子元件相邻的测试基因的表达。本讨论报告的野生型p53蛋白特异性DNA结合元件位于MCK增强子-启动子元件的p53响应区域内的鉴定。这个p53蛋白/DNA结合元件已经通过DNA酶I足迹分析确定，其鉴定了50-bp区域。这个50 bp的序列足以赋予野生型p53对异源最小启动子的反应性。p53蛋白的突变形式刺激这种DNA元件的能力要小得多。这项研究已经确定了第一个自然发生的野生型p53特异性DNA结合元件，能够介导测试基因的正调控的例子。结果表明野生型p53蛋白在基因调控中的生物学功能在突变型p53蛋白中丢失或改变。
It has been reported recently that the wild-type p53 gene product can positively regulate the expression of a test gene adjacent to the enhancer-promoter elements of the murine muscle-specific creatine kinase (MCK) gene. This discussion reports the identification of a wild-type p53 protein-specific DNA-binding element located within the p53-responsive region of the MCK enhancer-promoter element. This p53 protein/DNA-binding element has been defined by DNase I footprint analysis, which identified a 50-bp region. This 50-bp sequence was sufficient to confer wild-type p53 responsiveness on a heterologous minimal promoter. The mutant forms of p53 protein are much less capable of stimulating this DNA element. This study has identified the first example of a naturally occurring wild-type p53-specific DNA-binding element that is able to mediate positive regulation of a test gene. The results suggest a biological function in gene regulation for the wild-type p53 protein that is lost or altered in the mutant p53 proteins.