Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma.
Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma.
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DOI：
10.3109/10428194.2016.1160083
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发表时间：
2016-11
影响因子：
2.6
通讯作者：
Gilmore TD
中科院分区：
文献类型：
--
作者：
Haery L;Mussakhan S;Waxman DJ;Gilmore TD
组蛋白乙酰转移酶(HATS)突变是弥漫性大B细胞淋巴瘤(DLBCL)最常见的突变之一。我们之前的研究表明，两个人DLBCL细胞系RC-K8和SuDHL2表达C末端截短的、HAT结构域缺陷的p300蛋白(p300ΔC)，这是细胞最佳增殖所必需的。P300ΔC基因敲除后RC-K8细胞基因表达的微阵列分析显示，NF-κB和P53基因表达程序上调，MYC基因表达程序下调。实验表明，这些基因表达的改变是由于p300ΔC对NF-κB活性和P53蛋白水平的抑制以及对MYC蛋白水平的刺激，提示p300ΔC突变体通过调节细胞特异性癌蛋白的转录输出而促进DLBCL细胞的增殖。我们认为，p300/CBP基因截断代表了一类新的致癌突变，它优化了上下文特定的致癌转录因子的活性。我们提出了“致癌修饰物”来描述这种突变。
Mutations in histone acetyltransferases (HATs) are among the most common mutations in diffuse large B-cell lymphoma (DLBCL). We previously showed that two human DLBCL cell lines, RC-K8 and SUDHL2, express C-terminally truncated, HAT domain-deficient p300 proteins (p300ΔC) that are required for optimal cell proliferation. Microarray analysis of mRNA expression in RC-K8 cells following p300ΔC knockdown shows upregulation of NF-κB and p53 gene expression programs and down-regulation of a MYC gene expression program. Experiments indicate that these gene expression changes are due to inhibitory effects of p300ΔC on NF-κB activity and on p53 protein levels and stimulatory effects on MYC protein levels, suggesting that p300ΔC mutants enhance the proliferation of DLBCL cells by adjusting the transcriptional output of cell-specific oncoproteins. We propose that p300/CBP gene truncation represents a new class of oncogenic mutation that optimizes the activity of context-specific oncogenic transcription factors. We propose “oncogenic modifier” to describe such mutations.
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影响因子：
3.7
作者：
Kalaitzidis, D;Gilmore, TD
通讯作者：
Gilmore, TD
DOI：
10.1182/asheducation-2013.1.591
发表时间：
2013-12-01
影响因子：
3
作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
64.8
作者：
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通讯作者：
Pasqualucci, Laura