The t(8;21) fusion protein contacts co-repressors and histone deacetylases to repress the transcription of the p14ARF tumor suppressor
The t(8;21) fusion protein contacts co-repressors and histone deacetylases to repress the transcription of the p14ARF tumor suppressor
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DOI：
10.1016/s1079-9796(03)00021-4
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发表时间：
2003-03-01
影响因子：
2.3
通讯作者：
Linggi, B
中科院分区：
文献类型：
--
作者：
Hiebert, SW;Reed-Inderbitzin, EF;Linggi, B
t(8:2 1) 是与急性白血病相关的最常见的染色体易位之一。该易位将 AML1 的 DNA 结合域与几乎所有 ETO 共阻遏物融合。 ETO 与 mSin3 和 N-CoR 共阻遏物以及组蛋白脱乙酰酶 1、2 和 3 相关。尽管这是急性白血病中最常见的染色体易位之一，占急性髓性白血病 (AML) 病例的 10-15%，但刺激白细胞生成的转录调控的直接靶标尚不清楚。我们发现 AML1-ETO 在瞬时转染试验中抑制 p14(ARF) 肿瘤抑制因子的启动子，并降低多种细胞类型中 p14(ARF) 表达的内源水平。染色质免疫沉淀分析表明 AML1-ETO 与 p14(APF) 启动子结合。与其他急性髓系白血病相比，在含有 t(8;21) 的急性髓系白血病样本中，p14(ARF) mRNA 水平明显较低。因此，p14(ARF)是AML1-ETO的直接转录靶标。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
The t(8:2 1) is one of the most frequent chromosomal translocations associated with acute leukemia. The translocation fuses the DNA binding domain of AML1 to nearly all of the ETO co-repressor. ETO associates with the mSin3 and N-CoR co-repressors as well as histone deacetylases 1, 2, and 3. Although this is one of the most frequent chromosomal translocations in acute leukemia, accounting for 10-15% of the cases of acute myeloid leukemia (AML), the direct targets for transcriptional regulation that stimulate leukernogenesis are unknown. We found that AML1-ETO repressed the promoter of p14(ARF) tumor suppressor in transient transfection assays and reduced endogenous levels of p14(ARF) expression in multiple cell types. Chromatin immunoprecipitation assays demonstrated that AML1-ETO bound to the p14(APF) promoter. In acute myeloid leukemia samples containing the t(8;21), levels of p14(ARF) mRNA were markedly lower when compared to other acute myeloid leukemias. Therefore, p14(ARF) is a direct transcriptional target of AML1-ETO. (C) 2003 Elsevier Science (USA). All rights reserved.