MOLECULAR-CLONING AND FUNCTIONAL ANAL OF THE ADENOVIRUS E1A-ASSOCIATED 300-KD PROTEIN (P300) REVEALS A PROTEIN WITH PROPERTIES OF A TRANSCRIPTIONAL ADAPTER
MOLECULAR-CLONING AND FUNCTIONAL ANAL OF THE ADENOVIRUS E1A-ASSOCIATED 300-KD PROTEIN (P300) REVEALS A PROTEIN WITH PROPERTIES OF A TRANSCRIPTIONAL ADAPTER
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DOI：
10.1101/gad.8.8.869
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发表时间：
1994-04-15
影响因子：
10.5
通讯作者：
LIVINGSTON, DM
中科院分区：
文献类型：
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作者：
ECKNER, R;EWEN, ME;LIVINGSTON, DM
腺病毒E1A癌蛋白的生长控制功能取决于其与一组细胞蛋白相互作用的能力。其中包括视网膜母细胞瘤蛋白，p107，p130和p300。我们已经分离出编码全长人p300的cDNA，并将该基因的染色体定位于染色体22q13。p300含有三个富含半胱氨酸和组氨酸的区域，其中最羧基末端区域与E1A特异性相互作用。在它的中心，p300包含一个布罗莫结构域，这是某些转录辅激活因子的标志。我们已经检查了p300克服E1A对SV40增强子的抑制作用的能力。我们发现，p300分子缺乏一个完整的E1A结合位点可以绕过E1A的抑制和恢复到一个显着的程度上的SV 40增强子的活性，即使在高水平的E1A蛋白的存在下。这些结果表明，p300可能作为一个转录衔接蛋白的某些复杂的转录调控元件。
The growth-controlling functions of the adenovirus E1A oncoprotein depend on its ability to interact with a set of cellular proteins. Among these are the retinoblastoma protein, p107, p130, and p300. We have isolated a cDNA encoding full-length human p300 and mapped the chromosomal location of the gene to chromosome 22q13. p300 contains three cysteine- and histidine-rich regions of which the most carboxy-terminal region interacts specifically with E1A. In its center, p300 contains a bromodomain, a hallmark of certain transcriptional coactivators. We have examined the ability of p300 to overcome the repressive effect of E1A on the SV40 enhancer. We show that p300 molecules lacking an intact E1A-binding site can bypass E1A repression and restore to a significant extent the activity of the SV40 enhancer, even in the presence of high levels of E1A protein. These results imply that p300 may function as a transcriptional adaptor protein for certain complex transcriptional regulatory elements.