p53 transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300
p53 transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300
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DOI：
10.1074/jbc.m108870200
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发表时间：
2002-03-15
影响因子：
4.8
通讯作者：
Nyborg, JK
中科院分区：
文献类型：
--
作者：
Livengood, JA;Scoggin, KES;Nyborg, JK
肿瘤抑制因子p53募集细胞共激活因子CBP/p300介导靶基因的转录激活。在这项研究中，我们确定了一个新的CBP/p300，我们称之为CR2，位于羧基末端附近的p53相互作用区域。95个氨基酸的CR2区（氨基酸2055-2150）位于C/H3结构域附近，与CBP的最小类固醇受体辅激活因子1（SRC 1）相互作用结构域（也称为IBiD）精确对应。我们表明，该地区的p53参与C112相互作用驻留在前107个氨基酸的蛋白质。p53与CBP和高度同源的辅激活因子p300的CR2结构域强烈结合。重要的是，在全长p300蛋白中CR2的框内缺失强烈地损害了p300介导的体外染色质模板的p53转录激活。CBP/p300中p53相互作用的CR2结构域的鉴定促使我们询问是否也与CR2相互作用的人T细胞白血病病毒（HTLV-1）Tax蛋白与p53竞争结合到该结构域。我们发现，p53和税收表现出相互排斥的结合CR2区域，可能有助于以前报道的税收抑制p53功能。总之，这些研究确定并分子表征CBP/p300上的一个新的p53结合位点，该位点参与共激活因子介导的p53转录功能。p53.CR2相互作用的身份表明CBP/p300上至少有三个不同的位点可能参与介导p53反式激活。
The tumor suppressor p53 recruits the cellular coactivator CBP/p300 to mediate the transcriptional activation of target genes. In this study, we identify a novel p53-interacting region in CBP/p300, which we call CR2, located near the carboxyl terminus. The 95-amino acid CR2 region (amino acids 2055-2150) is located adjacent to the C/H3 domain and corresponds precisely with the minimal steroid receptor coactivator 1 (SRC1)-interacting domain of CBP (also called IBiD). We show that the region of p53 that participates in the C112 interaction resides within the first 107 amino acids of the protein. p53 binds strongly to the CR2 domain of both CBP and the highly homologous coactivator p300. Importantly, an in-frame deletion of CR2 within the full-length p300 protein strongly compromises p300-mediated p53 transcriptional activation from a chromatin template in vitro. The identification of the p53-interacting CR2 domain in CBP/p300 prompted us to ask if the human T-cell leukemia virus (HTLV-1) Tax protein, which also interacts with CR2, competes with p53 for binding to this domain. We show that p53 and Tax exhibit mutually exclusive binding to the CR2 region, possibly contributing to the previously reported Tax repression of p53 function. Together, these studies identify and molecularly characterize a new p53 binding site on CBP/p300 that participates in coactivator-mediated p53 transcription function. The identity of the p53.CR2 interaction indicates that at least three distinct sites on CBP/p300 may participate in mediating p53 transactivation.