TARGET FACULTY/SENESCENCE SIGNALING THROUGH P53

通过 P53 发出目标功能/衰老信号

• 批准号: 7381463
• 负责人: RONALD K GARY
• 金额: $ 18.81万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381463
• 关键词: TARGET; FACULTY; SENESCENCE; SIGNALING; THROUGH

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 necessarily killing the cells as a direct result of the chemical treatment. It is hoped that 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. We hypothesize that different modifications of p53 enable it to evoke cellular senescence under some circumstances and apoptosis, for example, under others. We plan to treat 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, we 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 antica

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。大多数化疗方法的目的通常是通过诱导细胞凋亡来杀死癌细胞。尚未充分研究的是癌细胞可能通过诱导细胞衰老而被迫停止增殖的可能性，而化学治疗不一定会直接杀死细胞。希望这样的策略能够产生更轻微的副作用，从而更好地被患者耐受。该项目旨在发现新的调节系统，介导类衰老途径以阻止细胞生长。人类肿瘤抑制因子p53在衰老调节中发挥着至关重要的作用。然而，p53 还协调其他细胞反应，例如细胞凋亡和 DNA 修复，并且尚不清楚共同的调节蛋白如何对这些不同的反应产生不同的影响。我们假设 p53 的不同修饰使其能够在某些情况下引起细胞衰老，并在其他情况下引起细胞凋亡。我们计划用各种诱导衰老或其他 p53 介导反应的药物治疗正常和癌性人类细胞，然后分析各种反应的分子特征。治疗后，我们将确定产生哪些 p53 翻译后修饰以及哪些 p53 依赖性转录反应被激活。通过将特定的生长抑制治疗与直接改变细胞生理学的独特分子特征联系起来，我们期望确定衰老途径的调控目标和分子标志，这将有助于开发一类新型抗衰老药物