Caspase-1 is a novel target of p63 in tumor suppression.
Caspase-1 is a novel target of p63 in tumor suppression.
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DOI：
10.1038/cddis.2013.175
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发表时间：
2013-05-23
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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作者：
p63是p53家族转录因子，除了在上皮发育中的独特作用外，其与其同系物p53共享肿瘤抑制活性。p63基因具有不同的转录起始位点，其产生两种N端异构体（反式激活结构域（TA）p63和氨基端截短蛋白（ΔN）p63）;此外，5′端的选择性剪接产生至少五种C端异构体。这种基因结构的复杂性可能引发了关于p63在癌症中功能的争论和争议，TP 63携带两个独特的启动子，编码TAp 63和Δ Np 63同种型，并具有离散的功能。然而，Δ Np 63还驱动在癌症和转移中具有相关作用的靶基因的表达。在这项研究中，我们确定了一个新的p63转录靶点，caspase-1。Caspase-1是促炎性caspase，其在肿瘤抑制中起作用。我们发现，这两种p63亚型促进caspase-1的表达，其启动子的物理结合。与我们的体外研究结果一致，我们还确定了人类癌症数据集中p63和caspase-1表达之间的直接相关性。此外，生存估计分析表明，p63和半胱天冬酶-1之间的功能相互作用代表了人类癌症中阳性生存结局的预测因子。总的来说，我们的数据报告了一个新的p63靶基因参与肿瘤抑制，临床分析强调了这一发现的生物学相关性，并提出了进一步的临床预测生物标志物。
p63 is a p53 family transcription factor, which besides unique roles in epithelial development, shares tumor suppressive activity with its homolog p53. The p63 gene has different transcriptional start sites, which generate two N-terminal isoforms (transactivation domain (TA)p63 and amino terminal truncated protein(ΔN)p63); in addition alternative splicing at the 5′-end give rise to at least five C-terminal isoforms. This complexity of gene structure has probably fostered the debate and controversy on p63 function in cancer, with TP63-harboring two distinctive promoters, codifying for the TAp63 and ΔNp63 isoforms, and having discrete functions. However, ΔNp63 also drives expression of target genes that have a relevant role in cancer and metastasis. In this study, we identified a novel p63 transcriptional target, caspase-1. Caspase-1 is proinflammatory caspase, which functions in tumor suppression. We show that both p63 isoforms promote caspase-1 expression by physical binding to its promoter. Consistent with our in vitro findings, we also identified a direct correlation between p63 and caspase-1 expression in human cancer data sets. In addition, survival estimation analysis demonstrated that functional interaction between p63 and caspase-1 represents a predictor of positive survival outcome in human cancers. Overall, our data report a novel p63 target gene involved in tumor suppression, and the clinical analysis underlines the biological relevance of this finding and suggests a further clinically predictive biomarker.
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将转录因子识别为单一的同源物2作为前列腺癌中潜在的生物标志物和免疫疗法靶标。
DOI：
10.1158/1078-0432.ccr-09-0911
发表时间：
2009-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arredouani MS;Lu B;Bhasin M;Eljanne M;Yue W;Mosquera JM;Bubley GJ;Li V;Rubin MA;Libermann TA;Sanda MG
通讯作者：
Sanda MG
DOI：
10.1073/pnas.1016814108
发表时间：
2010-12-14
影响因子：
11.1
作者：
Hu, Bo;Elinav, Eran;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
12.4
作者：
Kogan-Sakin, I.;Tabach, Y.;Rotter, V.
通讯作者：
Rotter, V.
影响因子：
82.9
作者：
Gonfloni, Stefania;Di Tella, Lucia;Cesareni, Gianni
通讯作者：
Cesareni, Gianni
DOI：
10.1186/bcr3171
发表时间：
2012-04-20
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dusek RL;Bascom JL;Vogel H;Baron S;Borowsky AD;Bissell MJ;Attardi LD
通讯作者：
Attardi LD