Functions of a novel suppressor of oncogenic Ras

一种新的癌基因Ras抑制因子的功能研究 致癌性Ras占所有人类癌症的30%以上。Ras通常控制有丝分裂途径 并起到控制细胞增殖的开/关开关的作用。异染色质似乎是一种形式的细胞 在果蝇和人类中，致癌Ras必须克服这一限制以诱导细胞增殖。许多肿瘤 抑制子，如Rb和BRCA，在异染色质形成中起作用，并且不能形成 异染色质形成本身允许肿瘤发生，以响应致癌Ras。但如何 异染色质形成抵消致癌Ras以及Ras如何克服异染色质介导的 肿瘤抑制仍不清楚。了解异染色质如何抵消致癌信号， 致癌途径如何克服异染色质诱导生长和增殖可能导致新的 表观遗传癌症疗法 为了研究致癌突变与表观遗传学改变之间的联系，我们使用了果蝇 遗传学，以确定新的球员介导细胞反应致癌Ras，特别注意 非常规Ras信号传导组分。在新的致癌Ras抑制因子中，我们发现， CRIF调节细胞增殖和异染色质形成。该项目的目标是 了解假定的肿瘤抑制因子CRIF拮抗致癌基因的作用的机制， Ras对细胞增殖的影响。这项研究的长期目标是阐明异染色质的形成 在表观遗传肿瘤抑制中的作用以及癌蛋白如何重组染色质以诱导细胞凋亡 增殖和肿瘤发生。我们假设CRIF通过抑制细胞增殖来抵消致癌Ras。 增殖和增加异染色质形成，表观遗传肿瘤抑制系统。在这 建议，我们计划阐明CRIF在抵消致癌Ras诱导的 增殖和异染色质调节。具体来说，我们将研究CRIF如何抵抗致癌Ras 在控制增殖中的作用，以及CRIF在调节异染色质中的作用。这些研究的结果将 为研究致癌基因的表观遗传效应的分子机制开辟了新的基础， Ras、表观遗传失调在癌症发展中的作用以及异染色质在肿瘤中的作用 镇压

Functions of a novel suppressor of oncogenic Ras Oncogenic Ras accounts for more than 30% of all human cancers. Ras normally controls mitogenic pathways and functions as an on/off switch controlling cell proliferation. Heterochromatin appears to be a form of cellular restraint in both flies and humans that oncogenic Ras has to overcome to induce cell proliferation. Many tumor suppressors, such as Rb and BRCAs, play a role in heterochromatin formation, and an inability to form heterochromatin formation itself permits tumorigenesis in response to oncogenic Ras. However, how heterochromatin formation counteracts oncogenic Ras and how Ras can overcome heterochromatin-mediated tumor suppression remain unclear. Understanding how heterochromatin counteracts oncogenic signals and how oncogenic pathways overcome heterochromatin to induce growth and proliferation may lead to novel epigenetic cancer therapeutics. To investigate the connection from oncogenic mutations to epigenetic alterations, we have used Drosophila genetics to identify new players mediating cellular responses to oncogenic Ras, with a particular attention to nonconventional Ras signaling components. Among the novel suppressors of oncogenic Ras, we found that CRIF regulates both cell proliferation and heterochromatin formation. The objective of this project is to understand the mechanism by which the putative tumor suppressor CRIF antagonizes the effects of oncogenic Ras on cell proliferation. The long-term goal of the research is to elucidate how heterochromatin formation functions in epigenetic tumor suppression and how oncoproteins reorganize chromatin to induce cell proliferation and tumorigenesis. We hypothesize that CRIF counteracts oncogenic Ras by inhibiting cell proliferation and increasing heterochromatin formation, an epigenetic tumor suppression system. In this proposal, we plan to elucidate the molecular functions CRIF in counteracting oncogenic Ras-induced proliferation and in heterochromatin regulation. Specifically, we will investigate how CRIF resist oncogenic Ras in controlling proliferation, and the role of CRIF in regulating heterochromatin. Results from these studies will break new grounds for investigating the molecular mechanisms underlying the epigenetic effects of oncogenic Ras, the role of epigenetic dysregulation in cancer development, and the role heterochromatin in tumor suppression.