MECHANISM & REGULATION OF BCL-2 ANTIPROLIFERATIVE EFFECT

描述：(改编自研究人员的摘要)程序化细胞 死亡，或称细胞凋亡，是一种活跃的细胞自杀形式 从生理上确保多余或不需要的细胞被消除。 癌蛋白，Bcl-2，在许多情况下对抗细胞凋亡，当 在恶性细胞中的表达通常会使化疗无效。BCL-2 也会引起对有丝分裂原刺激的细胞的暂时不耐受 但这种作用与其抗凋亡功能之间的关系是 之前没有澄清的。 在这项提案中，研究人员现在证明，事实上，Bcl-2 拥有两个独立的功能；即。它增加了细胞固有的 抵抗细胞程序性死亡，而且独立地也会延迟细胞 扩散。这表明了一种后生动物战略，在这种战略中， 具有细胞自主抗凋亡能力的细胞天生就受到限制， 并认为压倒一切的促有丝分裂信号和/或选择性地禁用 Bcl一2‘S抗增殖作用是Bcl一2增殖的必要条件 表达细胞。Bcl2基因与S基因表达的时间相关性 磷酸化及其对细胞增殖的影响表明了这一点 翻译后修饰可能代表一种这样的失活 机制。Bcl-2激酶启动的Bcl2‘S抗增殖剂失活 功能可能参与了Bcl2的继发性恶变 表现为惰性肿瘤，如滤泡性淋巴瘤。 他们提出的研究计划旨在检查Bcl2和S之间的关系 磷酸化对其抗增殖作用的影响，以鉴定该激酶 Bcl2‘S的磷酸化及其在恶性肿瘤中的作用 表达惰性肿瘤的Bcl2的转化。此外，该愿望 目的：探讨Bcl-2延缓细胞周期进程的机制。

DESCRIPTION: (adapted from the investigator's abstract) Programmed cell death, or apoptosis, is an active form of cellular suicide that functions physiologically to ensure that superfluous or unwanted cells are eliminated. The oncoprotein, Bcl-2, counters apoptosis in many instances, and when expressed in malignant cells often renders chemotherapy ineffective. Bcl-2 also provokes temporary refractoriness to mitogen stimulated cell proliferation but how this effect relates to its anti-apoptotic function was not previously clarified. In this proposal, the investigators now demonstrate that Bcl-2 in fact possesses two separate functions; ie. it increases a cell's inherent resistance against programmed cell death, and independently also delays cell proliferation. This suggests a metazoan strategy in which proliferation of cells with cell-autonomous resistance to apoptosis is inherently restricted, and argues that an overriding mitogenic signal and/or selective disabling of Bcl-2's antiproliferative effect is required for the proliferation of Bcl-2 expressor cells. The temporal correlation seen between Bcl-2's phosphorylation and its effect on cell proliferation suggests this post-translational modification may represent one such inactivation mechanism. Bcl-2 kinase initiated inactivation of Bcl-2's antiproliferative function may contribute to the secondary malignant transformations of Bcl-2 expressing indolent tumors, such as follicular lymphoma. Their proposed research program aims to examine the relation of Bcl-2's phosphorylation to its antiproliferative effect, to identify the kinase responsible for Bcl-2's phosphorylation and to examine its role in malignant transformation of Bcl-2 expressing indolent tumors. In addition, the wish to identify the mechanism by which Bcl-2 delays cell cycle progression.