The role of the pRB/E2F pathway in erythropoiesis and cell cycle control

pRB/E2F 通路在红细胞生成和细胞周期控制中的作用

• 批准号: nhmrc : 145803
• 负责人: Prof Patrick Humbert
• 金额: $ 18.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-prbe2f-pathway-cycle-control/77291
• 关键词: role; pRB; E2F; pathway; erythropoiesis

Circulating blood contains two major types of cells. Red blood cells supply the oxygen required by all cells in our body to survive and white blood cells protect our body from invasion by foreign organisms. The balance in the number of these cells in our blood is a carefully regulated process which, when disturbed, can lead to a number of life-threatening blood diseases. Uncontrolled overgrowth of blood cells results in a particular type of cancer known as leukaemia. In contrast, when there is an insufficient number of red blood cells, not enough oxygen reaches cells from the brain and other vital organs and results in a condition known as anaemia. We have genetically engineered a mouse that lack the protein known as E2F4 and is unable to produce enough red blood cells and suffers from anaemia. This protein, E2F4, controls genes essential for the decision of cells to start or stop growing and multiplying. The E2F4-deficient mice therefore provide a new and powerful model to understand the mechanism by which disturbance of red blood cell numbers can lead to diseases such as leukaemia and other diseases of the blood. Identification of the genes controlled by E2F4 may provide new targets for the development of therapeutic drugs to combat these diseases.

循环血液含有两种主要类型的细胞。红细胞提供我们体内所有细胞生存所需的氧气，白色细胞保护我们的身体免受外来生物的入侵。我们血液中这些细胞数量的平衡是一个精心调节的过程，当受到干扰时，可能导致许多危及生命的血液疾病。血细胞的不受控制的过度生长导致一种特殊类型的癌症，称为白血病。相比之下，当红细胞数量不足时，没有足够的氧气从大脑和其他重要器官到达细胞，导致贫血。我们已经通过基因工程改造了一只缺乏E2F4蛋白质的老鼠，它无法产生足够的红细胞，并患有贫血症。这种蛋白质E2F4控制着决定细胞开始或停止生长和繁殖所必需的基因。因此，E2F4缺陷小鼠提供了一个新的和强大的模型，以了解红细胞数量紊乱可能导致白血病和其他血液疾病的机制。鉴定E2F4控制的基因可能为开发治疗这些疾病的药物提供新的靶点。