SENESCENCE SIGNALING THROUGH P53

通过 P53 传递衰老信号

• 批准号: 7725220
• 负责人: RONALD K GARY
• 金额: $ 18.3万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725220
• 关键词: Adverse effects; Aftercare; Antineoplastic Agents; Apoptosis; Cancerous; Cell Aging; Cell physiology; Cells; Class; Computer Retrieval of Information on Scientific Projects Database; DNA Repair; Development; Funding; Grant; Growth; Human; Institution; Mediating; Modification; Molecular; Molecular Target; Pathway interactions; Patients; Play; Post-Translational Protein Processing; Proliferating; Protein p53; Regulation; Research; Research Personnel; Resources; Role; Signal Transduction; Source; System; TP53 gene; United States National Institutes of Health; cancer cell; cell growth; cell killing; genetic regulatory protein; killings; novel; response; senescence

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most chemotherapeutic approaches aim to kill cancer cells, usually by inducing apoptosis. Less well explored has been the possibility that cancer cells could be forced to stop proliferating, via induction of cellular senescence, without killing the cells. Such a strategy would produce milder side effects and therefore be better tolerated by patients. This project seeks to discover new regulatory systems that mediate senescence-like pathways to arrest cell growth. The human tumor suppressor p53 plays a vital role in the regulation of senescence. However, p53 also coordinates other cellular responses, such as apoptosis and DNA repair, and it is not known how these various responses are differentially effected by a common regulatory protein. Dr. Gary's lab hypothesizes that different modifications of p53 enable it to evoke cellular senescence under some circumstances and apoptosis, for example, under others. They are treating normal and cancerous human cells with various agents that induce senescence or other p53-mediated responses, and then analyze the molecular features of the various responses. After treatments, they will determine which post-translational modifications of p53 are produced and which p53-dependent transcriptional responses become activated. By connecting specific growth-arresting treatments to the distinct molecular features that direct changes in cellular physiology, we expect to identify regulatory targets and molecular hallmarks of the senescence pathway that will aid development of a novel class of anticancer drug.

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