Cyclin D1/CDK4 Complex in Hepatocyte Proliferation

描述(申请人提供)：本申请中提出的研究将进一步探讨细胞周期蛋白D1在肝细胞增殖、生长、代谢和基因调控中的作用。细胞周期蛋白D1是一种关键的细胞周期控制蛋白，也是一种重要的癌基因，在许多人类肿瘤中过表达。我们以前的研究已经证明，细胞周期蛋白D1在肝细胞增殖中起关键作用。这里概述的研究将进一步确定细胞周期蛋白D1在细胞周期进程、生长和我们实验室发现的新功能中的作用机制--调节肝脏代谢和控制信使核糖核酸稳定性。我们将确定细胞周期蛋白D1的功能结构域在每个过程中的作用。我们的方法将涉及到转基因技术和转基因小鼠的广泛使用，并旨在为我们对细胞周期蛋白D1在体内的作用的理解提供重大进展。我们期望这些研究将与肝脏再生、肝脏代谢和癌变过程高度相关。与公共健康相关：这项建议研究了细胞周期蛋白Cyclin D1的细胞活动，这是一种关键的细胞周期控制蛋白，在许多人类癌症中发挥作用。这些研究将更好地了解控制肝脏再生和促进癌症发展的机制。这些数据将有助于确定肝病和癌症治疗的潜在目标。

DESCRIPTION (provided by applicant): The studies proposed in this application will further investigate the role of cyclin D1 in hepatocyte proliferation, growth, metabolism and gene regulation. Cyclin D1 is a pivotal cell cycle control protein and an important oncogene that is over-expressed in many human cancers. Our previous studies have demonstrated that cyclin D1 plays a key role in hepatocyte proliferation. The studies outlined here will further define the mechanisms underlying the role of cyclin D1 in cell cycle progression, growth, and novel functions uncovered in our laboratory - the regulation of hepatic metabolism and the control of mRNA stability. We will define the role of functional domains of cyclin D1 in each of these processes. Our approach will involve the extensive use of transfection techniques and transgenic mice, and are intended to provide a significant advance in our understanding of the role of cyclin D1 in vivo. We expect that these studies will be highly relevant to the processes of liver regeneration, hepatic metabolism, and carcinogenesis. PUBLIC HEALTH RELEVANCE: This proposal examines the cellular actions of cyclin D1, a critical cell cycle control protein that plays a role in many human cancers. These studies will provide a better understanding of mechanisms that control liver regeneration and contribute to the development of cancer. This data will help to define potential targets for therapies for liver diseases and cancer.