A role for the tumour suppressor gene p53 in regulating neuronal apoptosis.
A role for the tumour suppressor gene p53 in regulating neuronal apoptosis.
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DOI：
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发表时间：
1997-10
期刊：
影响因子：
1.7
通讯作者：
P. Hughes;T. Alexi;S. Schreiber
中科院分区：
文献类型：
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作者：
P. Hughes;T. Alexi;S. Schreiber
肿瘤抑制基因p53是一种核磷蛋白，其正确的功能对于DNA损伤的适当细胞反应至关重要。有人认为，p53可能作为一个“基因组的监护人”，因为当DNA损伤是温和的，p53的功能，以停止细胞周期的进展，允许DNA修复发生之前，通过细胞周期的进展。这防止了在复制过程中将损伤“固定”到基因组中。然而，当DNA损伤严重且不可逆时，p53诱导细胞发生凋亡。最近的研究表明，损伤后神经元内DNA断裂和p53表达增加。似乎p53表达可能先于DNA片段化，这表明p53表达实际上可能引发神经元凋亡，导致DNA片段化，而不是在神经元中响应于DNA损伤而被诱导。最近的报道记录了来自p53基因缺失小鼠（p53-/-）的神经元在体外和体内对兴奋性毒性和DNA损伤剂的抗性，并显示p53过表达在体外诱导神经元凋亡，这支持了肿瘤抑制基因p53在调节神经元凋亡中的作用。在这里，我们回顾了最近的证据，并讨论可能的机制参与p53介导的神经元凋亡。
The tumour suppressor gene p53 is a nuclear phosphoprotein whose correct functioning is crucial for an appropriate cellular response to DNA damage. It has been suggested that p53 may act as a 'guardian of the genome' since when DNA damage is mild, p53 functions to halt cell cycle progression allowing DNA repair to occur before progression through the cell cycle. This prevents 'fixing' of lesions into the genome during replication. However when DNA damage is severe and irreversible, p53 induces the cell to undergo apoptosis. Recent studies have demonstrated DNA fragmentation and increased expression of p53 within neurons after injury. It appears that p53 expression may precede DNA fragmentation suggesting that rather than being induced in neurons in response to DNA damage, p53 expression may actually initiate neuronal apoptosis leading to DNA fragmentation. Recent reports documenting the resistance of neurons derived from p53-null mice (p53-/-) to excitotoxicity and DNA damaging agents both in vitro and in vivo and showing that p53 overexpression induces neuronal apoptosis in vitro support a role for the tumour suppressor gene p53 in regulating neuronal apoptosis. Here we review the recent evidence and discuss likely mechanisms involved in p53-mediated neuronal apoptosis.