THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY

ARF-P53 肿瘤抑制信号通路

• 批准号: 7369087
• 负责人: Michael G. Fried
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369087
• 关键词: ARF; P53; TUMOR; SUPPRESSOR; SIGNALING

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. The ARF-p53 tumor suppressor pathway is one of the cell?s major defenses against the stimulation of uncontrolled cell division induced by activated cellular and viral oncogene. ARF and/or p53 are mutated in over 70% of human cancers. The inappropriate activation of growth promoting cellular signaling pathways by oncogenes can result in the induction of ARF. The expression of ARF can activate p53 leading to apoptotic cell death or cell cycle arrest. The mechanisms by which the ARF-p53 pathway is regulated remains to be precisely elucidated. The expression of ARF can activate p53 leading to apoptotic cell death or cell cycle arrest. We have shown that the polyoma virus oncogene, PYMT, activates an ARF-induced p53 mediated block. We find that the polyoma virus small T-antigen, PYST, via its ability to bind to cellular protein phosphatase 2A (PP2A), can negate the ARF-induced block to cell division induced by PYMT. We intend to use the PY induction and inhibition of ARF signaling to p53 to better define this important tumor suppressor pathway. Our hypothesis is that the polyoma virus proteins are revealing an important new aspect of the ARF-p53 tumor suppressor signaling circuit, and we plan to use these viral proteins as tools to study its molecular basis. To better define the role of PYMT in activating ARF and as an oncogene, and to define the role of PYST in blocking ARF signaling to p53 we plan to characterize the proteins complexed to PYMT, PYST and members of the ARF-p53 signaling pathway. In the first instance proteins bound to TAP fusion constructs would be identified by Mass Spectrometry.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。 ARF-P53肿瘤抑制途径是细胞的主要防御能力之一，以防止激活的细胞和病毒癌基因诱导的不受控制的细胞分裂。 ARF和/或p53在超过70％的人类癌症中突变。癌基因促进细胞信号通路的不当激活可能会导致ARF诱导。 ARF的表达可以激活p53导致凋亡细胞死亡或细胞周期停滞。 ARF-P53途径受调节的机制仍有旨在精确阐明。 ARF的表达可以激活p53导致凋亡细胞死亡或细胞周期停滞。我们已经表明，多瘤病毒癌基因PYMT激活了ARF诱导的p53介导的块。我们发现，通过与细胞蛋白磷酸酶2a（PP2A）结合的能力，多瘤病毒小型T-抗原Pyst可以抵消PYMT诱导的细胞分裂的ARF诱导的块。我们打算将PY诱导和抑制ARF信号传导对p53更好地定义这一重要的肿瘤抑制途径。我们的假设是多瘤病毒蛋白正在揭示ARF-P53肿瘤抑制器信号传导回路的重要新方面，我们计划使用这些病毒蛋白作为研究其分子基础的工具。为了更好地定义PYMT在激活ARF和作为癌基因中的作用，并定义了PYST在阻止ARF信号传导到p53中的作用，我们计划表征与PYMT，PYST和ARF-P53信号通路的蛋白质。首先，将蛋白质与TAP融合构建体结合在一起，将通过质谱识别。