CO-ACTIVATOR FUNCTION IN ORAL CANCER CELLS

口腔癌细胞中的共激活剂功能

• 批准号: 6379970
• 负责人: Dennis J. McCance
• 金额: $ 27.12万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379970
• 关键词: DNA binding protein; cell differentiation; cell growth regulation; cell transformation; gel mobility shift assay; gene mutation; genetic regulation; genetic transcription; human papillomavirus; interleukin 6; keratinocyte; microarray technology; mutant; neoplastic cell; oncoprotein p21; oral pharyngeal neoplasm; protein structure function; representational difference analysis; tissue /cell culture; transcription factor; virus protein

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.

描述（改编自调查员的摘要）：共同激活剂CBP P300调节与细胞控制有关的基因的转录 周期和分化。虽然对执行的功能知之甚少 通过这些因素在角化形成细胞的分化中，申请人 使用病毒癌基因提供CBP/p300的初步数据 重要角色。人乳头瘤病毒16的E6蛋白（E6.16） 抑制角质形成细胞分化，申请人最近表明 E6.16蛋白在三个不同区域（C/H1，C/H3， 和一个C末端域）。相互作用抑制了CBP-P300的能力 与同一域结合的共激活转录因子。重要的是， 申请人已经确定了结合单个区域的E6.16的突变，该突变是 可用于研究单个域的功能而没有 破坏CBP/P300的其他功能。申请人建议使用这些 突变蛋白研究CBP/p300在角质形成细胞中的作用 分化，以确定需要哪些共激活因子 用于控制的分化，并研究CBP和P300是否 必要的。 CBP/P300的已知目标，其功能已与 将研究角质形成细胞分化，以及CBP/P300的新靶 将被确定。