Control of cell growth and size by a novel cell cycle checkpoint mechanism

通过新型细胞周期检查点机制控制细胞生长和大小

• 批准号: 8624497
• 负责人: Douglas R. Kellogg
• 金额: $ 30.84万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-17 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8624497
• 关键词: Biochemistry; Biological; Biology; Cell Cycle; Cell Cycle Checkpoint; Cell Shape; Cell Size; Cell division; Cells; Cellular biology; Clinic; Complex; Defect; Dissociation; Elements; Ensure; Eukaryotic Cell; Excision; Genetic; Growth; Guanosine Triphosphate Phosphohydrolases; In Vitro; Link; Malignant Neoplasms; Membrane; Mitosis; Mitotic; Modeling; Monitor; Nature; Normal Cell; Output; Pathology; Phosphorylation; Protein Kinase C; Protein Phosphatase 2A Regulatory Subunit PR53; Proteins; Reading; Shapes; Signal Transduction; Site; Solutions; Testing; Translating; Vesicle; Work; base; cancer cell; cell growth; in vivo; in vivo imaging; inhibitor/antagonist; innovation; killings; novel; public health relevance; reconstitution; research study; single cell analysis

The mechanisms that control cell growth and size are largely unknown and represent a fundamental unsolved problem in biology. We recently discovered a checkpoint that links mitotic entry to membrane growth. Our analysis of this checkpoint suggests a novel hypothesis: we propose that vesicles arriving at a site of membrane growth generate a checkpoint signal that is proportional to the extent of membrane growth. We further hypothesize that downstream components read the strength of this signal to determine when sufficient growth has occurred for entry into mitosis. This hypothesis suggests a simple and broadly relevant solution to two fundamental problems in cell biology: 1) How is cell size controlled? and 2) How is membrane growth integrated with the cell cycle? The proposed Aims test key predictions of the hypothesis. Aim 1 uses diverse approaches, including single cell analysis, to test whether membrane growth is translated into a proportional checkpoint signal. Aim 2 tests whether key checkpoint components translate a gradually increasing checkpoint signal into a switch-like output that triggers mitosis. Completion of the Aims will define a novel checkpoint mechanism that could control the size and shape of all eukaryotic cells.

控制细胞生长和大小的机制在很大程度上未知，代表了基本未解决的机制 生物学问题。我们最近发现了一个将有丝分裂条目与膜生长联系起来的检查点。我们的 该检查点的分析提出了一个新的假设：我们提出，囊泡到达了 膜生长产生一个与膜生长程度成正比的检查点信号。我们 进一步假设下游组件读取该信号的强度以确定何时足够 进入有丝分裂已经发生了增长。该假设提出了一个简单且广泛相关的解决方案 细胞生物学的两个基本问题：1）细胞尺寸如何控制？ 2）膜的生长如何 与细胞周期集成？提出的目标是对假设的关键预测。 AIM 1使用多样 方法，包括单细胞分析，以测试是否将膜生长转化为比例 检查点信号。 AIM 2测试关键检查点组件是否会逐渐增加检查点 信号进入触发有丝分裂的开关样输出。目标的完成将定义一个新颖的检查站 可以控制所有真核细胞的大小和形状的机制。