Viral Oncoprotein Inhibition of Quiescence

病毒癌蛋白对静止的抑制

• 批准号: 7647592
• 负责人: DAVID Morse LIVINGSTON
• 金额: $ 45.18万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647592
• 关键词: Cell Cycle; Development; Growth Factor; Knowledge; Link; Malignant Neoplasms; Molecular; Neoplastic Cell Transformation; Normal Cell; Oncogene Proteins; Papovaviridae; Pathway interactions; Performance; Process; Proliferating; Property; Protein Phosphatase 2A Regulatory Subunit PR53; Signal Transduction Pathway; Therapeutic; Viral; Work; cancer cell; deprivation; transforming virus; tumor

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DNA肿瘤病毒SV40的急性感染可以促使静止的哺乳动物细胞进入细胞周期。 这项工作的至少一部分是由两种病毒癌蛋白之一的 SV40 LT 完成的。其余执行 由另一种癌蛋白 SV40 ST 产生。 ST 在​​此过程中的作用取决于其干扰的能力 蛋白磷酸酶 PP2A 的功能，PP2A 是已知的人类肿瘤抑制基因的产物。 出乎意料的是，静息控制的 SV40 ST 扰动的至少部分机制是 针对 G2（或 G2/M）中发生的事件。 ST 在​​ G2 期间的目标过程依赖于 PP2A 并且必须保持完整，以便细胞在下一个 G1 期启动有丝分裂原剥夺后静止。还 涉及的是 p130/E2F4/DREAM 复合体，其完整性依赖于 PP2A，该复合体具有 已被证明可以在维持静止状态中发挥作用。是否以 G2 为中心的 PP2A 功能和/或 PP2A 功能在细胞周期的另一个时间运行，与该复合体通信以获取许可 静止状态不明。拟议研究的主旨旨在了解 1）如何在分子中 术语，G2 静止控制过程运行，2) 其扰动是否有助于 SV40 STdependent 肿瘤转化和肿瘤发生，3）如果是这种情况，它的扰动如何引起 这些影响。