CO-ACTIVATOR FUNCTION IN ORAL CANCER CELLS

描述(改编自《调查者摘要》)：共同激活者CBP 和p300调节参与细胞控制的基因的转录。 循环和分化。尽管人们对所执行的功能知之甚少 通过角质形成细胞分化过程中的这些因素，申请人 利用病毒癌基因提供了CBP/p300发挥作用的初步数据 重要的角色。人乳头瘤病毒16型E6蛋白(E6.16) 抑制角质形成细胞分化，申请人最近表明 E6.16蛋白与CBP和p300在三个不同的区域(C/H1，C/H3， 和C-末端结构域)。这种相互作用抑制了CBP-p300的作用 共同激活与相同结构域结合的转录因子。重要的是 申请人已经确定了E6.16的突变，这些突变结合了单个区域， 可用于研究单个域的功能，而不需要 扰乱CBP/p300的其他功能。申请者建议使用这些 突变蛋白研究CBP/p300在角质形成细胞中的作用 区分，以确定需要哪些共激活子结构域 用于受控分化，并研究CBP和p300是否都是 这是必要的。CBP/p300的已知靶点，其功能已被牵涉到 角质形成细胞分化的研究，以及CBP/p300的新靶点 将会被确认。

DESCRIPTION (Adapted from the Investigator's Abstract): The co-activators CBP and p300 regulate transcription of genes involved in the control of the cell cycle and differentiation. Although little is known of the functions performed by these factors in the differentiation of keratinocytes, the applicant provides preliminary data, using viral oncogenes, that CBP/p300 play an important role. The E6 protein (E6.16) from human papillomavirus type 16 inhibits keratinocyte differentiation and the applicant has recently shown that E6.16 protein binds to both CBP and p300 in three distinct regions (C/H1, C/H3, and a C-terminal domain). The interaction inhibits the ability of CBP-p300 to co-activate transcription factors that bind to the same domains. Importantly, the applicant has identified mutations of E6.16 that bind single regions, which can be used to investigate the function of individual domains without disrupting other functions of CBP/p300. The applicant proposes to use these mutant proteins to investigate the role of CBP/p300 in keratinocyte differentiation, to determine which domains of the co-activators are required for controlled differentiation, and to study if both CBP and p300 are necessary. Known targets of CBP/p300, whose function has been implicated in keratinocyte differentiation will be studied, and novel targets of CBP/p300 will be identified.