CELL CYCLE REGULATION DURING STRESS

压力期间的细胞周期调节

• 批准号: 6288714
• 负责人: MYRIAM none GOROSPE
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6288714
• 关键词: RNA binding protein; apoptosis; biological signal transduction; cell cycle; cell growth regulation; cyclins; gene expression; human tissue; messenger RNA; oncoprotein p21; regulatory gene; stress; tissue /cell culture; tumor suppressor genes; RNA binding protein; apoptosis; biological signal transduction; cell cycle; cell growth regulation; cyclins; gene expression; human tissue; messenger RNA; oncoprotein p21; regulatory gene; stress; tissue /cell culture; tumor suppressor genes

Stressful signals are transduced through various signalling pathways, ultimately resulting in the altered expression of critical genes, including cycle regulatory genes. While transcriptional events regulating gene expression has been thoroughly studied, it is becoming increasingly clear that post-transcriptional regulatory mechanisms also play a critical role in gene regulation by stress. These post- transcriptional processes, still poorly understood, include mRNA processing, transport, stability and translation, as well as post- translational events such as protein processing, phosphorylation and degradation. With respect to mRNA stability, we are investigating the mechanisms regulating the expression of various cell cycle regulatory molecules. Expression of p21, an inhibitor of cyclin-dependent kinases, is induced by various stresses (such as ultraviolet light) through stabilization of its mRNA. Expression of various cyclins throughout the cell division cycle and in response to stress agents is likewise regulated through alterations in the half-life of their respective mRNA. Much effort is focused on searching for RNA regions and proteins involved in regulating the stability of p21, cyclins and other cell cycle regulatory genes. This analysis involves both in vitro and in vivo determinations of RNA binding and RNA degradation, the identification of the RNA-binding proteins involved and the signalling pathways that modulate their activity. We are also studying the function of the tumor suppressor gene von Hippel-Lindau (VHL) as it is believed to modulate gene expression at the levels of transcription elongation, mRNA stability and protein degradation. We are examining the function of the VHL tumor suppressor gene within the stress response. - cyclins, p21, mRNA stability, mRNA-binding proteins, apoptosis, growth arrest, VHL

应力信号通过各种信号通路转导，最终导致关键基因的表达改变，包括循环调节基因。虽然对调节基因表达的转录事件进行了彻底的研究，但越来越清楚的是，转录后调节机制在压力通过压力调节基因调节中也起着关键作用。这些转录后过程仍然尚未了解，包括mRNA处理，运输，稳定性和翻译，以及翻译后事件，例如蛋白质加工，磷酸化和降解。关于mRNA稳定性，我们正在研究调节各种细胞周期调节分子表达的机制。 p21的表达是细胞周期蛋白依赖性激酶的抑制剂，通过稳定其mRNA诱导了各种应力（例如紫外线）。在整个细胞分裂周期中的各种细胞周期蛋白的表达同样通过改变其各自mRNA的半衰期的变化来调节。大量精力集中在寻找参与调节p21，细胞周期蛋白和其他细胞周期调节基因稳定性的RNA区域和蛋白质。该分析涉及RNA结合和RNA降解的体外和体内测定，所涉及的RNA结合蛋白的鉴定以及调节其活性的信号传导途径。我们还研究了肿瘤抑制基因von Hippel-lindau（VHL）的功能，因为据信可以调节基因表达在转录伸长，mRNA稳定性和蛋白质降解水平上。我们正在检查应力反应中VHL肿瘤抑制基因的功能。 - 细胞周期蛋白，p21，mRNA稳定性，mRNA结合蛋白，凋亡，生长停滞，VHL