Bioflavonoid apigenin induces phosphorylation of p53

生物类黄酮芹菜素诱导 p53 磷酸化

• 批准号: 7154511
• 负责人: RUKIYAH VAN DROSS
• 金额: $ 15.21万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-10 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7154511
• 关键词: DNA binding protein; SDS polyacrylamide gel electrophoresis; apoptosis; casein kinase; chemoprevention; cyclin dependent kinase; cyclins; flavones; flavonoids; genetic transcription; mitogen activated protein kinase; p53 gene /protein; phosphorylation; protein protein interaction; serine; transcription factor; ultraviolet radiation; western blottings

DESCRIPTION (provided by applicant): This application for a K01 Mentored Career Development Award for Underrepresented Minorities is being submitted by Dr. Rukiyah Van Dross (Principal Investigator) and Dr. Jill C. Pelling (Sponsor). The application consists of two Phases for career development: Phase I (mentored, dependent) will consist of two-years of continuing postdoctoral supervision for Dr. Van Dross by Dr. Pelling, and Phase II (mentored, independent) consisting of 3 years of continued research by Dr. Van Dross in a more independent fashion as a research assistant professor in the Department of Pathology and Laboratory Medicine, but still working in space adjacent to Dr. Pelling's research laboratory with continued mentoring by Dr. Pelling. In Phase I Dr. Van Dross will work as a postdoctoral investigator in Dr. Pelling's laboratory, continuing to develop independent research skills in experimental design, data interpretation, manuscript/grant writing, graduate student/technician supervision, travel to scientific meetings and development of contacts with colleagues in the field of carcinogenesis and chemoprevention for purposes of establishing future research collaborations and developing a network of colleagues in the field who can advise Dr. Van Dross. The research project that Dr. Van Dross will work on during Phase I of her career development plan is presented in detail in this application, and is focused on specific aims to investigate the role of p38 MAP kinase in modulation of chemopreventive action by the bioflavonoid apigenin. This research project has been developed by Dr. Van Dross in consultation with Dr. Pelling, and its goals are clearly relevant to cancer biology and chemoprevention. The experimental approach proposed by Dr. Van Dross will extend her preliminary observations on apigenin induction of p38 MAP kinase and concomitant phosphorylation of p53 protein and apoptosis. The research proposed in this K01 application is separate from Dr. Pelling's NIH grant CA72987-05, entitled "Molecular mechanism of chemoprevention by apigenin," which focuses on induction of ERK by apigenin and downstream effects on p53 post-translational modification. In Phase II of the career development plan, Dr. Van Dross will be promoted to research assistant professor in the Department of Pathology and Laboratory Medicine (see Chairman's letter), assuming continued productivity toward research goals of the K01 grant. In Phase II Dr. Van Dross will continue to be mentored by Dr. Pelling in her research as well as in grant writing skills, manuscript writing, reviewing journal articles and professional contacts in her field. The research carried out by Dr. Van Dross during Phase II of her career development plan is outlined in detail in this application and will focus on investigating the protein/protein interactions of p38 MAP kinase and p53 and their role in apoptosis. The long-term goal of Dr. Van Dross' career development plan is to provide her with the skills to develop, establish and manage an independent externally-funded research program as a tenure-track faculty member at an academic medical center.

描述（由申请人提供）：本申请由Rukiyah Van Dross博士（首席研究员）和Jill C. Pelling博士（发起人）提交。申请包括两个阶段的职业发展：第一阶段（指导，依赖）将包括佩林博士对范·德罗斯博士的两年博士后继续监督，第二阶段（指导，独立）包括范·德罗斯博士以更独立的方式继续研究三年，作为病理和实验室医学系的研究助理教授，但仍然在佩林博士的研究实验室附近的空间工作，继续由佩林博士指导。在第一阶段，Van Dross博士将作为博士后研究员在Pelling博士的实验室工作，继续在实验设计、数据解释、手稿/拨款写作、研究生/技术员监督等方面发展独立的研究技能。参加科学会议，并与致癌和化学预防领域的同事建立联系，以便建立未来的研究合作，并在该领域建立一个可以向Van Dross博士提供建议的同事网络。Van Dross博士将在她职业发展计划的第一阶段进行的研究项目在本申请中详细介绍，并专注于研究p38 MAP激酶在生物类黄酮芹菜素调节化学预防作用中的作用。这项研究项目是由Van Dross博士与Pelling博士共同制定的，其目标显然与癌症生物学和化学预防有关。Van Dross博士提出的实验方法将扩展她对芹菜素诱导p38 MAP激酶以及伴随的p53蛋白磷酸化和细胞凋亡的初步观察。该K01申请中提出的研究是独立于Pelling博士的NIH拨款CA72987-05，题为“apigenin化学预防的分子机制”，其重点是通过apigenin诱导ERK以及对p53翻译后修饰的下游影响。在职业发展计划的第二阶段，Van Dross博士将被提升为病理和检验医学系的研究助理教授（见主席的信），假设继续为K01基金的研究目标工作。在第二阶段，Van Dross博士将继续受到Pelling博士的指导，包括她的研究、拨款写作技巧、手稿写作、审查期刊文章和她所在领域的专业联系。Van Dross博士在其职业发展计划的第二阶段进行的研究在本申请中详细概述，并将重点研究p38 MAP激酶和p53的蛋白质/蛋白质相互作用及其在细胞凋亡中的作用。Van Dross博士职业发展计划的长期目标是为她提供发展、建立和管理一个独立的外部资助的研究项目的技能，作为一个学术医疗中心的终身教职员工。