DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein
DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein
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DOI：
10.1126/science.1068712
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发表时间：
2002-04-19
期刊：
影响因子：
56.9
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
--
作者：
Tran, H;Brunet, A;Greenberg, ME
从磷酸肌醇3-激酶到蛋白激酶Akt的信号通路通过抑制转录因子的FOXO家族成员的活性来控制无脊椎动物中的生物体寿命和哺乳动物中的细胞存活和增殖。我们发现，哺乳动物FOXO 3a也在细胞周期中的G（2）到M检查点发挥作用，并触发受损DNA的修复。通过基因阵列分析，FOXO 3a被发现在G（2）-M检查点调节几个基因的表达，这些基因调节细胞对应激的反应。生长停滞和DNA损伤反应基因Gadd 45 a似乎是FOXO 3a的直接靶点，其介导FOXO 3a对DNA修复的部分作用。这些发现表明，在哺乳动物中，FOXO 3a通过诱导DNA修复来调节细胞对应激的抵抗力，从而也可能影响生物体的寿命。
The signaling pathway from phosphoinositide 3-kinase to the protein kinase Akt controls organismal life-span in invertebrates and cell survival and proliferation in mammals by inhibiting the activity of members of the FOXO family of transcription factors. We show that mammalian FOXO3a also functions at the G(2) to M checkpoint in the cell cycle and triggers the repair of damaged DNA. By gene array analysis, FOXO3a was found to modulate the expression of several genes that regulate the cellular response to stress at the G(2)-M checkpoint. The growth arrest and DNA damage response gene Gadd45a appeared to be a direct target of FOXO3a that mediates part of FOXO3a's effects on DNA repair. These findings indicate that in mammals FOXO3a regulates the resistance of cells to stress by inducing DNA repair and thereby may also affect organismal life-span.