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: 6017099
• 负责人: Xavier Grana
• 金额: $ 11.12万
• 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/6017099
• 关键词: cell cycle; cell growth regulation; cyclin dependent kinase; cyclins; enzyme activity; enzyme induction /repression; enzyme inhibitors; gene targeting; laboratory mouse; phosphoprotein phosphatase; phosphorylation; 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是视网膜母细胞瘤家族的一员， 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。 该系列 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还参与了 几种类型的癌症表明，其相关的同行，p107 和p130也可能有牵连。事实上，p130基因定位于 在一组人类肿瘤中发现16号染色体缺失。 虽然pRb是最具特征的肿瘤抑制蛋白之一， 对p107和p130的了解很少。我们的研究结果表明，p130是 在细胞周期中受到调节。特别是，我们观察到， 在G 0/G1转换时p130磷酸化状态的变化， 在G1中后期。 本申请中提出的实验旨在 在了解机制和蛋白质参与调节 p130在G 0/G1期和细胞周期中的表达。 其目的是 我们的建议是：1、确定cyclin/CDK全酶是否参与 在细胞周期中p130的磷酸化。2、要定性 参与p130去磷酸化的蛋白磷酸酶。3, 为了确定在细胞周期中p130的磷酸化是否 调节其与其他细胞蛋白的结合。4、确定 口袋蛋白之间存在功能关系， 尤其是pRb和p130之间。一旦我们实现这些目标， 深入了解我们对G 0/G1过渡调节的理解 和对细胞周期的承诺。