Les empreintes génétiques : nouvel outil en médecine légale
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- 作者：Audrey Mansuet-Lupo ; Vé ; ronique Van Huffel ; Philippe Rouger
- 关键词：P53 ; Mdm2 ; Premature aging ; Mouse aging model
- 刊名：Medecine et Droit
- 出版年：2008
- 出版时间：January-February 2008
- 年：2008
- 卷：2008
- 期：88
- 页码：24-28
- 全文大小：277 K
文摘
Evidence has accumulated that p53, a prototypical tumor suppressor, may also influence aspects of organismal aging. We have previously described a p53 mutant mouse model, the p53+/m mouse, which is cancer resistant yet exhibits reduced longevity and premature aging phenotypes. p53+/m mice express one full length p53 allele and one truncated p53 allele that is translated into a C-terminal fragment of p53 termed the M protein. The augmented cancer resistance and premature aging phenotypes in the p53+/m mice are consistent with a hyperactive p53 state. To determine how the M protein could increase p53 activity, we examined the M protein in various cellular contexts. Here, we show that embryo fibroblasts from p53+/m mice exhibit reduced proliferation and cell cycle progression compared to embryo fibroblasts from p53+/− mice (with equivalent wild-type p53 dosage). The M protein interacts with wild-type p53, increases its stability, and facilitates its nuclear localization in the absence of stress. Despite increasing p53 stability, the M protein does not disrupt p53–Mdm2 interactions and does not prevent p53 ubiquitination. These results suggest molecular mechanisms by which the M protein could influence the aging and cancer resistance phenotypes in the p53+/m mouse.