Viral Oncoprotein Inhibition of Quiescence

病毒癌蛋白对静止的抑制

• 批准号: 8233033
• 负责人: DAVID Morse LIVINGSTON
• 金额: $ 44.63万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233033
• 关键词: Acute; Cell Cycle; Cells; Complex; DNA Tumor Viruses; Development; Event; G1 Phase; Growth Factor; Human; Infection; Knowledge; Licensing; Link; Maintenance; Malignant Neoplasms; Mammalian Cell; Mitogens; Molecular; Neoplastic Cell Transformation; Normal Cell; Oncogene Proteins; Papovaviridae; Pathway interactions; Process; Proliferating; Property; Protein Phosphatase 2A Regulatory Subunit PR53; Protein phosphatase; Research; Rest; Role; Signal Transduction Pathway; Simian virus 40; Therapeutic; Time; Tumor Suppressor Genes; Viral; Work; cancer cell; deprivation; transforming virus; tumor; tumorigenesis

Acute infection by the small DNA tumor virus, SV40, can drive quiescent mammalian cells into the cell cycle. At least part of this work is performed by SV40 LT, one of the two viral oncoproteins. The rest is performed by the other oncoprotein, SV40 ST. The role of ST in this process depends upon its ability to interfere with the function of the protein phosphatase, PP2A, the product of a known human.tumor suppressing gene. Unexpectedly, at least part of the mechanism underlying SV40 ST perturbation of quiescence control is directed at events that occur in G2 (or G2/M). The process targeted by ST during G2 is PP2A- dependent and must be intact for cells to quiesce following mitogen deprivation initiated during the next G1 phase. Also involved is the p130/E2F4/DREAM complex, the integrity of which is PP2A dependent, This complex has been shown to operate in the maintenance of quiescence. Whether G2-centered PP2A function and/or PP2A function operating at another time(s) during the cell cycle communicates with this complex to license quiescence is unclear. The thrust of the proposed research is aimed at understanding 1) how, in molecular terms, the G2 quiescence control process operates, 2) whether its perturbation contributes to SV40 STdependent neoplastic transformation and tumorigenesis and 3), if this is the case, how its perturbation elicits these effects.

小型DNA肿瘤病毒SV40的急性感染可以将静止的哺乳动物细胞驱动到细胞周期中。 这项工作的至少一部分是由两个病毒癌蛋白之一SV40 LT进行的。其余的 由另一种癌蛋白Sv40 ST。 ST在此过程中的作用取决于其干扰的能力 蛋白质磷酸酶PP2A的功能，是已知人类的抑制基因的乘积。 出乎意料的是，静态控制的SV40 ST扰动至少一部分机制是 针对G2（或G2/M）中发生的事件。 G2期间ST靶向的过程是PP2A-依赖性的 并且必须完好无损地使细胞在下一个G1期间启动有丝分裂原剥夺后quiesce。还 涉及的是P130/E2F4/Dream Complex 已显示在静止的维持中起作用。以G2为中心的PP2A功能和/或 PP2A功能在细胞周期期间另一个时间运行 静止尚不清楚。拟议研究的推力旨在理解1）如何在分子中 术语，G2静止控制过程的运作，2）其扰动是否有助于SV40 STDETICONTENT 肿瘤转化和肿瘤发生以及3），如果是这种情况，它的扰动如何引起 这些影响。