MDM2 EXPRESSION IS INDUCED BY WILD TYPE-P53 ACTIVITY
MDM2 EXPRESSION IS INDUCED BY WILD TYPE-P53 ACTIVITY
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DOI：
10.1002/j.1460-2075.1993.tb05678.x
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发表时间：
1993-02-01
期刊：
影响因子：
11.4
通讯作者：
OREN, M
中科院分区：
文献类型：
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作者：
BARAK, Y;JUVEN, T;OREN, M
我们最近的特点是一个95 kDa的蛋白质，p95，表现出增强的结合温度敏感的p53（ts-p53）时，细胞被转移到32.5 ℃，温度下，ts-p53具有野生型（wt）样的活动。在本研究中，我们表明，p95是mdm 2假定的原癌基因的产物。在维持在32.5 ℃的细胞中，mdm 2与ts-p53的复合物形成增强是由于温度变化后总mdm 2蛋白水平升高。我们进一步证明，mdm 2表达的诱导野生型p53活性是在mRNA水平。该诱导以非常快速的动力学发生，并且不需要从头蛋白质合成，表明p53直接参与该过程。基于这些数据和最近的研究结果暗示p53作为一种转录因子，我们认为mdm 2基因是野生型p53激活的目标。鉴于mdm 2作为p53活性的特异性拮抗剂的能力，该诱导过程可用于紧密地自动调节活细胞中的p53活性。
We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 32.5-degrees-C, a temperature at which ts-p53 possesses wild-type (wt)-like activities. In the present study we show that p95 is a product of the mdm2 putative proto-oncogene. The enhanced complex formation of mdm2 with ts-p53 in cells maintained at 32.5-degrees-C is due to an elevation in total mdm2 protein levels following the temperature shift. We further demonstrate that the induction of mdm2 expression by wt p53 activity is at the mRNA level. The induction occurs with very rapid kinetics and does not require de novo protein synthesis, suggesting a direct involvement of p53 in the process. Based on these data and on recent findings implicating p53 as a transcription factor, we suggest that the mdm2 gene is a target for activation by wt p53. In view of the ability of mdm2 to act as a specific antagonist of p53 activity, this induction process may serve to tightly autoregulate p53 activity in living cells.