摘要
当 p53 活动为瘤抑制被要求时，非强迫的 p53 活动在另一方面对有机体有害，导致不恰当的细胞的死亡或增长缺点。未受阻碍的 p53 活动在发展中的胚胎是致命的，加重对维持在在这个时期期间的 p53 活动的紧密的控制的需要。p53， Mdm2 和 Mdm4 的否定管理者的关键角色，在脊椎动物，开发由在老鼠与 Mdm2 和 Mdm4 基因删除被观察的 embryogenesis 的致命的混乱真相大白。胚胎的致命性仅仅由附加 p53 移动被救。这里，我们总结发生在肾开发的多重步的 Mdm2/Mdm4-p53 轴的贡献。有条件，房间类型特定的删除在肾的形态发生揭示这些蛋白质的不同功能。从指向的基因删除的肾的显型上的严重影响强调 Mdm2/Mdm4-p53 连结在 nephrogenesis 上起的关键作用，并且强调需要为肾函数缺点和联系心血管的机能障碍在这条小径与错误监视病人。
While p53 activity is required for tumour suppression, unconstrained p53 activity on the other hand is detrimental to the organism, resulting in inappropriate cellular death or proliferation defects. Unimpeded p53 activity is lethal in the developing embryo, under- lining the need for maintaining a tight control on p53 activity during this period. The critical role of the negative regulators of p53, Mdm2 and Mdm4, in vertebrate development came to light by fatal disruption of embryogenesis that was observed with Mdm2 and Mdm4 gene deletions in mice. Embryonic lethality was rescued only by superimposing p53 removal. Here we summarize the contri- bution of the Mdm2/Mdm4-p53 axis that occurs at multiple steps of kidney development. Conditional, cell type-specific deletions reveal distinct functions of these proteins in renal morphogenesis. The severe impact on the renal phenotype from targeted gene deletions underscores the critical role played by the Mdm2/Mdm4-p53 nexus on nephrogenesis, and emphasizes the need to monitor patients with aberrations in this pathway for kidney function defects and associated cardiovascular dysfunction.
