CREB-binding protein p300 are transcriptional coactivators of p65
CREB-binding protein p300 are transcriptional coactivators of p65
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DOI：
10.1073/pnas.94.7.2927
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发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
Collins, T
中科院分区：
文献类型：
--
作者：
Gerritsen, ME;Williams, AJ;Collins, T
CBP（CREB结合蛋白）和p300是连接转录激活子和基础转录器的多功能共激活子。在本研究中，我们鉴定CBP和p300是核因子KB（NF KB）组分p65（RelA）的共激活子。CBP和p300作为共激活因子的作用与此一致，CBP和p300都增强了E-选择素和VCAM-1-CAT报告基因构建体的p65激活转录。N-和C-末端结构域的CBP/p300功能相互作用与p65的区域含有转录激活结构域的哺乳动物双杂交试验证明。CBP/p300与p65的直接物理相互作用通过谷胱甘肽S-转移酶融合蛋白结合和免疫共沉淀/Western印迹研究证明。腺病毒E1 A12 S蛋白与CBP和p300复合，抑制p65依赖的基因表达。报告基因的表达可以通过CBP或p300的过表达从EIA抑制中拯救出来。CBP和p300作为p65驱动的基因激活的共激活因子，可能在苦参碱诱导的各种免疫和炎症基因的表达中发挥重要作用。
CBP (CREB-binding protein) and p300 are versatile coactivators that link transcriptional activators to the basal transcriptional apparatus, In the present study, we identify CBP and p300 as coactivators of the nuclear factor-KB (NF KB) component p65 (RelA). Consistent with their role as coactivators, both CBP and p300 potentiated p65-activated transcription of E-selectin and VCAM-1-CAT reporter constructs. The N- and C-terminal domains of both CBP/p300 functionally interact with a region of p65 containing the transcriptional activation domain as demonstrated by mammalian two-hybrid assays. Direct physical interactions of CBP/p300 with p65 were demonstrated by glutathione S-transferase fusion protein binding, and coimmunoprecipitation/Western blot studies. The adenovirus E1A 12S protein, which complexes with CBP and p300, inhibited p65-dependent gene expression. Reporter gene expression could be rescued from EIA inhibition by overexpression of CBP or p300. CBP and p300 act as coactivators of p65-driven gene activation and may play an important role in the cytokine-induced expression of various Immune and inflammatory genes.