RNA TUMOR VIRUS/HEMATOPOIETIC CELLS INTERACTIONS

描述（改编自申请人摘要）：研究重点是 Abelson小鼠白血病病毒（Ab-MLV）诱导 淋巴瘤和转化淋巴样细胞。 Abl在触发中的作用 生长，抑制凋亡和驱动肿瘤抑制因子的选择 将检查Tp 53和Mts 1中的突变。 四个具体目标将 处理。 第一个检查了TP 53突变的选择，包括 突变的类型，它们产生的动力学以及 推动他们的选择。 第二个具体目标是研究改变的 与Ab-MLV相关的p16蛋白在体内和体外的表达 介导转化 第三个具体目标是利用最近 发现了Ab-MLV突变体，它不刺激生长，但抑制 凋亡 这种突变导致Bcl-x蛋白的变化， 切割PARP，ICE蛋白酶的底物。 这些途径 将检测v-Abl诱导这些信号并抑制细胞凋亡。 的 最后一个具体的目的是研究v-Abl破坏控制的机制， G1过境。

DESCRIPTION (Adapted from Applicant's Abstract): The research focuses on the mechanism by which Abelson murine leukemia virus (Ab-MLV) induces lymphomas and transforms lymphoid cells. The role of Abl in triggering growth, suppressing apoptosis and driving the selection of tumor suppressor mutations in Tp53 and Mts1 will be examined. Four specific aims will addressed. The first examines the selection of Tp53 mutations, including the type of mutations, the kinetics at which they arise and the forces that drive their selection. The second specific aim studies the altered expression of p16 protein in vivo and in vitro, as it relates to Ab-MLV mediated transformation. The third specific aim utilizes a recently discovered Ab-MLV mutant which does not stimulate growth but does suppress apoptosis. This mutant leads to changes in the Bcl-x protein and altered cleavage of PARP, a substrate for the ICE proteases. The pathways by which v-Abl induces these signals and suppresses apoptosis will be examined. The last specific aim studies the mechanism by which v-Abl disrupts control of G1 transit.