A viral mechanism for inhibition of p300 and PCAF acetyltransferase activity
A viral mechanism for inhibition of p300 and PCAF acetyltransferase activity
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DOI：
10.1016/s0092-8674(00)80552-8
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发表时间：
1999-02-05
期刊：
影响因子：
64.5
通讯作者：
Evans, RM
中科院分区：
文献类型：
--
作者：
Chakravarti, D;Ogryzko, V;Evans, RM
核小体组蛋白修饰被认为是激活RNA聚合酶II依赖性转录的关键步骤。p300/CBP和PCAF组蛋白乙酰转移酶（HAT）是几种转录因子的共激活因子，包括核激素受体、p53和Stat 1 α，并通过形成激活复合物和促进组蛋白乙酰化来参与转录。腺病毒E1 A癌蛋白通过与p300/CBP结合并从复合物中置换PCAF和p/CIP蛋白来抑制转录信号传导。在这里，我们表明，E1 A直接抑制HAT活性的p300/CBP和PCAF在体外和p300依赖的转录在体内。此外，E1 A抑制PCAF复合物对核小体组蛋白的修饰，并阻断p53乙酰化。这些结果表明HAT活性的调节是一种新的转录调节机制。
Nucleosomal histone modification is believed to be a critical step in the activation of RNA polymerase II-dependent transcription. p300/CBP and PCAF histone acetyltransferases (HATs) are coactivators for several transcription factors, including nuclear hormone receptors, p53, and Stat1 alpha, and participate in transcription by forming an activation complex and by promoting histone acetylation. The adenoviral E1A oncoprotein represses transcriptional signaling by binding to p300/CBP and displacing PCAF and p/CIP proteins from the complex. Here, we show that E1A directly represses the HAT activity of both p300/CBP and PCAF in vitro and p300-dependent transcription in vivo. Additionally, E1A inhibits nucleosomal histone modifications by the PCAF complex and blocks p53 acetylation. These results demonstrate the modulation of HAT activity as a novel mechanism of transcriptional regulation.