An anti-apoptotic role for the p53 family member, p73, during developmental neuron death
An anti-apoptotic role for the p53 family member, p73, during developmental neuron death
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DOI：
10.1126/science.289.5477.304
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发表时间：
2000-07-14
期刊：
影响因子：
56.9
通讯作者：
Miller, FD
中科院分区：
文献类型：
--
作者：
Pozniak, CD;Radinovic, S;Miller, FD
p53 发挥重要的促凋亡作用，这一功能被认为与其家族成员 p73 和 p63 共有。在这里，我们发现p73主要以截短的亚型存在于发育中的神经元中，当交感神经元在神经生长因子（NGF）撤除后凋亡时，其水平急剧下降。截短的 p73 表达增加可将这些神经元从 NCF 撤除或 p53 过表达诱导的细胞凋亡中拯救出来。在p73-/-小鼠中，p73的所有亚型都被删除，发育中的交感神经元的凋亡大大增强。因此，截短的 p73 是神经元中必需的抗凋亡蛋白，可以抵消 p53 的促凋亡功能。
p53 plays an essential pro-apoptotic role, a function thought to be shared with its family members p73 and p63. Here, we show that p73 is primarily present in developing neurons as a truncated isoform whose levels are dramatically decreased when sympathetic neurons apoptose after nerve growth factor (NGF) withdrawal. Increased expression of truncated p73 rescues these neurons from apoptosis induced by NCF withdrawal or p53 overexpression. In p73-/- mice, all isoforms of p73 are deleted and the apoptosis of developing sympathetic neurons is greatly enhanced. Thus, truncated p73 is an essential anti-apoptotic protein in neurons, serving to counteract the pro-apoptotic function of p53.