Modulation of mammalian life span by the short isoform of p53
Modulation of mammalian life span by the short isoform of p53
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DOI：
10.1101/gad.1162404
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发表时间：
2004-02-01
影响因子：
10.5
通讯作者：
Scrable, H
中科院分区：
文献类型：
--
作者：
Maier, B;Gluba, W;Scrable, H
p53的短异构体（p44）的过度表达意外地揭示了p53在小鼠体型和寿命调控中的作用。p44对胰岛素样生长因子（IGF）信号轴的过度激活启动了一个激酶级联反应，该级联反应通过p21Cip1抑制潜在的无限制生长。这表明，已知在低等生物中调节寿命的基因活性通路在哺乳动物中通过p53与控制细胞增殖的机制相联系。因此，p53短异构体和长异构体的适当表达可能在肿瘤抑制和组织再生之间维持平衡，这是哺乳动物长寿的一个主要必要条件。
Overexpression of the short isoform of p53 (p44) has unexpectedly uncovered a role for p53 in the regulation of size and life span in the mouse. Hyperactivation of the insulin-like growth factor (IGF) signaling axis by p44 sets in motion a kinase cascade that clamps potentially unimpeded growth through p21Cip1. This suggests that pathways of gene activity known to regulate longevity in lower organisms are linked in mammals via p53 to mechanisms for controlling cell proliferation. Thus, appropriate expression of the short and long p53 isoforms might maintain a balance between tumor suppression and tissue regeneration, a major requisite for long mammalian life span.