A naturally occurring 4-bp deletion in the intron 4 of p53 creates a spectrum of novel p53 isoforms with anti-apoptosis function.
A naturally occurring 4-bp deletion in the intron 4 of p53 creates a spectrum of novel p53 isoforms with anti-apoptosis function.
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p53 内含子 4 中自然发生的 4-bp 缺失产生了一系列具有抗凋亡功能的新型 p53 亚型
DOI：
10.1093/nar/gku1359
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发表时间：
2015-01
影响因子：
14.9
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Shi H;Tao T;Huang D;Ou Z;Chen J;Peng J
p53通过转录调节参与控制细胞增殖或凋亡的基因的表达而起肿瘤抑制因子的作用。p53及其亚型Δ 133 p53/Δ 113 p53形成负调控环，p53激活Δ 133 p53/Δ 113 p53的表达，而Δ 133 p53/Δ 113 p53特异性拮抗p53的凋亡活性。该途径对于保护胚胎发生过程尤其重要，因为DNA损伤信号或发育应激对p53的突然激活对发育中的胚胎是有害的。在这里，我们报告了五个新的p53亚型的鉴定。p53β是由于p53基因内含子8的选择性剪接而产生的，而其他四个，即TA 2 p53、TA 3 p53、TA 4p 53和TA 5 p53，是由Δ 113 p53基因内含子1（在p53基因内含子4内）的选择性剪接和斑马鱼中选择性剪接产物内天然存在的CATT 4 bp缺失的组合产生的。CATT 4 bp缺失产生四个翻译起始密码子，其与Δ 113 p53的开放阅读框同框。我们还发现，TAp 53与Δ 113 p53共享相同的启动子，并具有拮抗p53凋亡活性的功能。Δ 113 p53/TA 2/3/4/5 p53的鉴定揭示了一种促存活机制，该机制在胚胎发生期间响应于DNA损伤条件而稳健地发挥作用。
p53 functions as a tumor suppressor by transcriptionally regulating the expression of genes involved in controlling cell proliferation or apoptosis. p53 and its isoform Δ133p53/Δ113p53 form a negative regulation loop in that p53 activates the expression of Δ133p53/Δ113p53 while Δ133p53/Δ113p53 specifically antagonizes p53 apoptotic activity. This pathway is especially important to safeguard the process of embryogenesis because sudden activation of p53 by DNA damage signals or developmental stress is detrimental to a developing embryo. Here we report the identification of five novel p53 isoforms. p53β is generated due to alternative splicing of the intron 8 of p53 while the other four, namely, TA2p53, TA3p53, TA4p53 and TA5p53, result from the combination of alternative splicing of intron 1 (within intron 4 of the p53 gene) of the Δ113p53 gene and a naturally occurring CATT 4 bp deletion within the alternative splicing product in zebrafish. The CATT 4 bp deletion creates four translation start codons which are in-frame to the open reading frame of Δ113p53. We also show that TAp53 shares the same promoter with Δ113p53 and functions to antagonize p53 apoptotic activity. The identification of Δ113p53/TA2/3/4/5p53 reveals a pro-survival mechanism which operates robustly during embryogenesis in response to the DNA-damage condition.
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影响因子：
2
作者：
Chen, Jun;Peng, Jinrong
通讯作者：
Peng, Jinrong
影响因子：
8
作者：
Marcel, V.;Vijayakumar, V.;Hainaut, P.
通讯作者：
Hainaut, P.
影响因子：
--
作者：
Khoury, Marie P;Bourdon, Jean-Christophe
通讯作者：
Bourdon, Jean-Christophe
影响因子：
3.7
作者：
Tao T;Shi H;Huang D;Peng J
通讯作者：
Peng J
影响因子：
--
作者：
Davidson WR;Kari C;Ren Q;Daroczi B;Dicker AP;Rodeck U
通讯作者：
Rodeck U