ADENOVIRAL E1A-ASSOCIATED PROTEIN P300 AS A FUNCTIONAL HOMOLOG OF THE TRANSCRIPTIONAL COACTIVATOR CBP
ADENOVIRAL E1A-ASSOCIATED PROTEIN P300 AS A FUNCTIONAL HOMOLOG OF THE TRANSCRIPTIONAL COACTIVATOR CBP
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DOI：
10.1038/374085a0
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发表时间：
1995-03-02
期刊：
影响因子：
64.8
通讯作者：
GOODMAN, RH
中科院分区：
文献类型：
--
作者：
LUNDBLAD, JR;KWOK, RPS;GOODMAN, RH
265K核蛋白CBP最初被鉴定为蛋白激酶A(PKA)磷酸化形式的转录因子CREB(1)的共激活因子。CBP中参与CREB结合和转录激活的结构域与腺病毒E1A相关的细胞蛋白P300(参考文献2，3)以及秀丽线虫的两个假想蛋白质R10E11.1和K03H1.10(分别参考文献4和文献5)高度相关，其功能未知。在这里，我们证明了CBP和p300对PKA磷酸化形式的CREB具有相似的结合亲和力，并且在增强CREB激活的基因表达方面，p300可以替代CBP。我们发现，E1a通过p300酸保守的结构域与CBP结合，抑制了CBP和p300依赖CREB的共激活功能。我们的结果表明，与E1a相关的基因抑制和细胞永生化功能涉及一系列相关蛋白的失活，这些蛋白通常参与第二信使调节的基因表达。
THE 265K nuclear protein CBP was initially identified as a coactivator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB(1). The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral E1A-associated cellular protein p300 (refs 2, 3), and to two hypothetical proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show that CBP and p300 have similar binding affinity for the PKA-phosphorylated form of CREB, and that p300 can substitute for CBP in potentiating CREB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 acid represses the CREB-dependent co-activator functions of both CBP and p300. Our results indicate that the gene repression and cell immortalization functions associated with E1A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.