REGULATION OF P130 DURING THE CELL CYCLE AND QUIESCENCE

P130 在细胞周期和静止期间的调节

• 批准号: 2430508
• 负责人: Xavier Grana
• 金额: $ 13.85万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430508
• 关键词: cell cycle; cell growth regulation; cyclins; enzyme activity; enzyme induction /repression; enzyme inhibitors; gene targeting; laboratory mouse; phosphoprotein phosphatase; phosphorylation; protein kinase; retinoblastoma protein; tissue /cell culture; transcription factor; transfection; tumor suppressor genes

DESCRIPTION: p130 is a member of the retinoblastoma family of pocket proteins, which so far is represented by two other proteins, the retinoblastoma tumor suppressor protein (pRb) and p107. This family of proteins shares the ability to suppress growth in a variety of cell types and its members are believed to play a pivotal role in cell cycle control and differentiation. In addition, pRb has been implicated in the genesis of several types of cancer suggesting that its related counterparts, p107 and p130, may also be implicated. Indeed, the p130 gene maps to a region of chromosome 16 found deleted in a set of human tumors. Although pRb is one of the best characterized tumor suppressor proteins, very little is known about p107 and p130. Our results suggest that p130 is regulated during the cell cycle. In particular, we have observed major changes in the phosphorylation status of p130 at the G0/G1 transition and in mid-to-late G1. The experiments proposed in this application are aimed at understanding the mechanisms and proteins involved in the regulation of p130 at the G0/G1 transition and during the cell cycle. The aims of this proposal are: 1, to establish whether cyclin/CDK holoenzymes are involved in the phosphorylation of p130 during the cell cycle. 2, to characterize the protein phosphatase(s) involved in the dephosphorylation of p130. 3, to ascertain whether phosphorylation of p130 during the cell cycle regulates its association with other cellular proteins. 4, to determine the existence of functional relationships between pocket proteins, in particular between pRb and p130. Once we meet these aims, we will gain insights into our understanding of the regulation of the G0/G1 transition and the commitment to the cell cycle.

描述：p130是Pocket视网膜母细胞瘤家族的成员。 蛋白质，到目前为止由另外两种蛋白质代表， 视网膜母细胞瘤肿瘤抑制蛋白(PRb)和p107。这个家庭 蛋白质具有抑制多种细胞类型生长的能力。 它的成员被认为在细胞周期控制中起着关键作用 和差异化。此外，pRb还与该病的发生有关。 几种类型的癌症表明其相关的对应物，p107 和p130，也可能与此有关。事实上，p130基因映射到一个区域 在一组人类肿瘤中发现了缺失的16号染色体。 虽然pRb是最具特性的肿瘤抑制蛋白之一， 人们对p107和p130知之甚少。我们的结果表明，p130是 在细胞周期中进行调节。特别是，我们观察到了少校 P130在G0/G1期的磷酸化状态变化及 在G1中后期。本申请中提出的实验旨在 了解参与调节的机制和蛋白质 P130蛋白在G0/G1期和细胞周期中的表达。这样做的目的是 建议：1、确定是否涉及细胞周期蛋白/CDK全酶 在细胞周期中p130的磷酸化。2、要刻画 蛋白磷酸酶(S)参与了p130的去磷酸化。3、 为了确定p130在细胞周期中的磷酸化 调节其与其他细胞蛋白的结合。4，以确定 口袋蛋白之间存在功能关系，在 尤其是在pRb和p130之间。一旦我们实现了这些目标，我们就会获得 对我们对G0/G1转变调节的理解的见解 以及对细胞周期的承诺。