Regulation of G1-Specific Gene Expression in Yeast

酵母中 G1 特异性基因表达的调控

• 批准号: 7274749
• 负责人: CURT WITTENBERG
• 金额: $ 40.04万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7274749
• 关键词: Affect; Attention; Binding; Biological; Cell Cycle; Cell Cycle Progression; Cell Cycle Regulation; Cell Cycle Stage; Cell Proliferation; Cessation of life; Chromatin Remodeling Factor; Cyclin-Dependent Kinases; Cyclins; Defect; Disease; Eukaryotic Cell; Failure; Family; G1 Phase; Gene Expression; Gene Family; Genes; Genetic Transcription; Goals; Growth; In Vitro; Lead; Malignant Neoplasms; Nature; Numbers; Phosphorylation; Phosphotransferases; Physiological; Process; Regulation; Research; Research Personnel; Role; Signal Transduction; Transcriptional Activation; Transcriptional Regulation; Yeasts; base; chromatin remodeling; cyclin G1; genetic regulatory protein; in vivo; insight; novel; programs; promoter; research study; transcription factor

DESCRIPTION (provided by applicant): In most eukaryotic cells, G1 phase is the primary interval for integration of internal and environmental signals with the cell cycle apparatus. Failure to respond to those signals can lead to defects in proliferation that, in metazoans, may include malignancy and even death. One of the primary controls governing cell cycle progression is via coordinate regulation of a large family of G1-specific genes. Genes of that family encode numerous cell cycle regulators including G1 and S phase cyclins that promote progression through early stages of the cell cycle. Consequently, modulating expression of G1-specific genes is an efficient way of coordinately regulating many processes. In yeast, the G1-specific transcription program is activated by the G1 cyclin-associated cyclin dependent protein kinase, CIn3/CDK that activates promoter-associated SBF and MBF transcription factors via an unknown mechanism. The goal of the proposed research is understand the regulation G1-specific gene expression and the integration of transcriptional regulation with the cyclin/CDK machinery. This will be accomplished through discovery and characterization of novel regulators of SBF and MBF and by understanding the interaction of CIn/CDK with regulators of transcription. In Specific Aims 1 and 2, we propose to further characterize Whi5, which we recently described as negative regulator of SBF-dependent transcription antagonized by CIn3/CDK. In Specific Aim 3, we propose to identify and characterize novel regulators of SBF and MBF. Finally, in Specific Aim 4, we propose to establish the biological relevance of the interaction between the RSC chromatin-remodeling complex and G1 cyclins. We are hopeful that completion of the proposed research will provide a broad understanding of coordination of the cell cycle regulatory apparatus with the transcriptional machinery, thereby, enhancing our understanding of the control of cell proliferation in both normal and disease states.

描述（由申请人提供）：在大多数真核细胞中，G1相是将内部和环境信号与细胞周期设备整合的主要间隔。未能响应这些信号可能会导致扩散的缺陷，因为在后生动物中，可能包括恶性甚至死亡。控制细胞周期进程的主要控制之一是通过坐标调节大型G1特异性基因家族。该家族的基因编码了许多细胞周期调节剂，包括G1和S相细胞周期蛋白，它们通过细胞周期的早期阶段促进进展。因此，调节G1特异性基因的表达是协调调节许多过程的有效方法。在酵母中，G1特异性转录程序被G1 cyclin相关的细胞周期蛋白蛋白激酶，CIN3/CDK激活，该蛋白CIN3/CDK通过未知机制激活与启动子相关的SBF和MBF转录因子。拟议的研究的目的是了解调节G1特异性基因表达以及转录调控与细胞周期蛋白/CDK机械的整合。这将通过发现和对SBF和MBF的新调节剂的发现和表征来实现，并了解CIN/CDK与转录调节剂的相互作用。在特定目标1和2中，我们提出进一步表征WHI5，我们最近将其描述为由CIN3/CDK拮抗的SBF依赖性转录的负调节剂。在特定目标3中，我们建议识别和表征SBF和MBF的新型调节剂。最后，在特定的目标4中，我们建议建立RSC染色质复合复合物和G1细胞周期蛋白之间相互作用的生物学相关性。我们希望拟议的研究的完成将提供对细胞周期调节设备与转录机械的协调的广泛理解，从而增强了我们对正常和疾病状态中细胞增殖的控制的理解。