WILD-TYPE P53 CAN DOWN-MODULATE THE ACTIVITY OF VARIOUS PROMOTERS
WILD-TYPE P53 CAN DOWN-MODULATE THE ACTIVITY OF VARIOUS PROMOTERS
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DOI：
10.1073/pnas.88.22.9979
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发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
OREN, M
中科院分区：
文献类型：
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作者：
GINSBERG, D;MECHTA, F;OREN, M
野生型（wt）p53蛋白是肿瘤抑制基因的产物，在许多类型的肿瘤中，肿瘤抑制基因是失活的常见靶点。该蛋白质的核定位以及其他特征表明它可能参与基因表达的调节。为了探索这种可能性，在许多系统中研究了过量产生的wt p53的影响。通过wt p53的抗增殖作用诱导生长停滞极大地损害了细胞在血清刺激后表现出c-fos mRNA增加的能力。用p53表达质粒与连接到各种启动子的报告基因一起共转染细胞的实验表明，野生型p53可以有效地减少来自血清诱导基因的一系列启动子的转录，但不能减少来自主要组织相容性复合体基因的转录。p53介导的c-fos基因表达的抑制甚至发生在放线菌酮的存在下。动力学研究表明，野生型p53的效果是快速的，而不是代表生长停滞的次要后果。这些发现支持p53在转录调控中的作用，可能是通过减少正在进行的细胞增殖所需的基因表达。
The wild-type (wt) p53 protein is the product of a tumor suppressor gene that is a frequent target for inactivation in many types of tumors. The nuclear localization of the protein, as well as additional features, suggest that it may be involved in the regulation of gene expression. To explore this possibility, the effects of overproduced wt p53 were investigated in a number of systems. Induction of growth arrest via the antiproliferative effect of wt p53 greatly impaired the ability of cells to exhibit an increase in c-fos mRNA upon serum stimulation. Experiments in which cells were cotransfected with p53 expression plasmids together with a reporter gene linked to various promoters revealed that wt p53 could effectively reduce transcription from a series of promoters derived from serum-inducible genes, but not from a major histocompatibility complex gene. The p53-mediated repression of c-fos gene expression occurred even in the presence of cycloheximide. Kinetic studies indicate that the effect of wt p53 is rapid, rather than representing a secondary consequence of growth arrest. These findings support a role for p53 in transcriptional regulation, perhaps by reducing the expression of genes that are needed for ongoing cell proliferation.