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Regulation of histone acetyltransferase activity of p300 and PCAF by proto-oncogene protein DEK

机译:原癌基因蛋白DEK对p300和PCAF组蛋白乙酰转移酶活性的调节

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摘要

The proto-oncogene protein DEK has been implicated in the t(6;9) chromosomal translocation associated with a subtype of acute myelogenous leukemia (AML), which results in the formation of a DEK-CAN fusion protein. Histone acetylation is an important post-translational modification which is involved in transcriptional regulation. In this study, we report that the acidic domain containing protein DEK interacts with histones and exerts a potent inhibitory effect on both p300 and PCAF-mediated histone acetyltransferase activity and transcription. Using chromatin immunoprecipitation assays, we have demonstrated that the recruitment of DEK to the appropriate promoter induces the histone H3 and H4 hypoacetylation of chromatin. Collectively, our data illustrate the important regulatory role played by protein DEK in transcriptional regulation, and suggest that transcription-regulating acidic domain regions may play a role in leukemogenesis. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
机译:原癌基因蛋白DEK已与与急性骨髓性白血病(AML)的亚型相关的t(6; 9)染色体易位有关,导致DEK-CAN融合蛋白的形成。组蛋白乙酰化是重要的翻译后修饰,其参与转录调控。在这项研究中,我们报告含有酸性域的蛋白质DEK与组蛋白相互作用,并且对p300和PCAF介导的组蛋白乙酰转移酶活性和转录均具有有效的抑制作用。使用染色质免疫沉淀测定法,我们已经证明DEK募集到适当的启动子会诱导染色质的组蛋白H3和H4低乙酰化。总的来说,我们的数据说明了蛋白DEK在转录调控中所起的重要调控作用,并暗示转录调控的酸性结构域可能在白血病发生中起作用。 (c)2006年欧洲生物化学学会联合会。由Elsevier B.V.发布。保留所有权利。

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