Cyclin D1/CDK4 Complex in Hepatocyte Proliferation

描述（由申请人提供）：本申请中提出的研究将进一步研究细胞周期蛋白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是一种重要的细胞周期调控蛋白，也是一种重要的癌基因，在许多人类癌症中过度表达。我们以前的研究表明，细胞周期蛋白D1在肝细胞增殖中起着关键作用。本文概述的研究将进一步确定细胞周期蛋白D1在细胞周期进展、生长和我们实验室发现的新功能中的作用机制--肝脏代谢的调节和mRNA稳定性的控制。我们将定义在这些过程中的每一个细胞周期蛋白D1的功能域的作用。我们的方法将涉及广泛使用的转染技术和转基因小鼠，并打算提供一个显着的进步，我们的理解细胞周期蛋白D1在体内的作用。我们期望这些研究将与肝再生、肝代谢和致癌过程高度相关。公共卫生相关性：该提案研究了细胞周期蛋白D1的细胞活动，细胞周期蛋白D1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靶点。

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.