Roles for HCF-1 in cell proliferation/differentiation

HCF-1 在细胞增殖/分化中的作用

• 批准号: 6920653
• 负责人: HAIYUAN DING
• 金额: $ 4.83万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6920653
• 关键词: RNA interference; apoptosis; cell differentiation; cell growth regulation; cell proliferation; gel mobility shift assay; genetic transcription; immunoprecipitation; neoplastic process; postdoctoral investigator; protein protein interaction; protein structure function; transcription factor

DESCRIPTION (provided by applicant): To gain insight into the roles of HCF-1 in cell cycle control, biochemical and genetic approaches will be combined to study the interaction between HCF-1 and the Myc/Max/Mad transcription factor network that plays a central role in controlling cellular proliferation, differentiation, and apoptosis. The specific aims are: (1) To probe HCF-1-Mad interactions; (2) To determine whether HCF-1-Mad interactions affect the transcription properties of Mad; and (3) To study the influence of HCF-1-Mad interaction on cell proliferation and differentiation. Specifically, immunoprecipitation will be used to analyze the association of HCF-1 with Mad, and whether this association is affected by other proteins, such as Max, Myc, and Sin3. Electrophoretic mobility shift assays will be used to examine the DNA-binding activity of the HCF-1-Mad complex, and in vivo transcription activity assays will provide information about roles of HCF-1 in modulating the activity of Mad. Small interfering RNAs will be used to deplete endogenous Mad and study the activities of mutant forms of Mad that are defective in HCF-1 association. These studies will reveal the biological roles of HCF-1 and Myc-Max-Mad network in cell proliferation, differentiation, and cancer progression.

描述（由申请人提供）：为了深入了解HCF-1在细胞周期控制中的作用，将结合生物化学和遗传学方法来研究HCF-1与Myc/Max/Mad转录因子网络之间的相互作用，该网络在控制细胞增殖、分化和凋亡中起核心作用。具体目标是：（1）探讨HCF-1-Mad相互作用;（2）确定HCF-1-Mad相互作用是否影响Mad的转录特性;（3）研究HCF-1-Mad相互作用对细胞增殖和分化的影响。具体而言，免疫沉淀将用于分析HCF-1与Mad的关联，以及这种关联是否受到其他蛋白质（如Max，Myc和Sin 3）的影响。 电泳迁移率变动分析将用于检查HCF-1-Mad复合物的DNA结合活性，并且体内转录活性分析将提供关于HCF-1在调节Mad活性中的作用的信息。小干扰RNA将被用来消耗内源性Mad和研究突变形式的Mad的活动是有缺陷的HCF-1协会。这些研究将揭示HCF-1和Myc-Max-Mad网络在细胞增殖、分化和癌症进展中的生物学作用。