CONTROL OF STEM CELL PROLIFERATION BY CELL CYCLE INHIBITORS

细胞周期抑制剂对干细胞增殖的控制

• 批准号: 6652847
• 负责人: James M Roberts
• 金额: $ 20.94万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652847
• 关键词: cell cycle; cell cycle proteins; cell proliferation; cyclin dependent kinase; enzyme inhibitors; fibronectins; gene targeting; growth factor; growth inhibitors; hematopoietic stem cells; laboratory mouse

Progression through the mitotic cell cycle is driven by the enzymatic activity of protein kinases known as the cyclin dependent kinases (CDKs). The activity of these kinases is normally kept in check in quiescent cells by another family of proteins, the cyclic kinase inhibitors, which bind and inactivate CDKs. This project will focus on a cyclic kinase inhibitor, p27kip1, which we have previous shown acts to limit proliferation in hematopoietic cells. The proposed experiments will determine whether loss of p27, in our p27 knockout mice, will lead to abnormal cell proliferation in hematopoietic stem cells. We will use both in vitro and in vivo methods to determine whether p27 normally regulates the proliferation of stem cells in response to soluble growth factors or the extracellular matrix protein, fibronectin. The potential for p27 to cooperate with other cell cycle inhibitory proteins in the control of stem cell proliferation will also be investigated.

有丝分裂细胞周期的进程是由被称为周期蛋白依赖激酶（CDKs）的蛋白激酶的酶活性驱动的。这些激酶的活性通常在静止细胞中被另一种蛋白质家族所控制，即环激酶抑制剂，它结合CDKs并使其失活。该项目将重点关注环激酶抑制剂p27kip1，我们之前已经证明它可以限制造血细胞的增殖。我们提出的实验将确定p27基因敲除小鼠中p27的缺失是否会导致造血干细胞中细胞增殖异常。我们将使用体外和体内两种方法来确定p27是否在可溶性生长因子或细胞外基质蛋白纤维连接蛋白的作用下正常调节干细胞的增殖。p27与其他细胞周期抑制蛋白合作控制干细胞增殖的潜力也将被研究。