Transcriptional complexity of cell cycle regulated genes during cell division and tumorigenesis

大规模的转录组和基因组注释工作最近已经确定了所有编码蛋白磷酸化细胞机制的基因。已发现哺乳动物中激酶和磷酸酶的分子网络的大小比以前报道的复杂得多，许多激酶和磷酸酶基因座平均每个基因产生超过4个转录本。该基金旨在利用全系统方法研究转录复杂性在控制正常细胞分裂和肿瘤发生中的作用。而不是依赖于基于基因座的研究，该提案旨在采取系统生物学方法，解决扩展的人类磷酸调节蛋白质组的功能多样性，识别在正常细胞周期和/或肿瘤进展中积极和动态表达的网络的所有组件，然后筛选具有调节细胞周期能力的选定新组件。这些研究将促进我们对蛋白磷酸化机制参与调节细胞分裂的理解，突出潜在相关肿瘤发生的新组分，并可能确定新的化疗靶点。

Massive scale transcriptome and genome annotation efforts have recently identified all genes encoding the cellular machinery of protein phosphorylation. The size of the molecular network of kinases and phosphatses has been found to be far more complex in mammals than previously reported, with many kinase and phosphatase loci generating, on average, more than 4 transcripts per gene. This grant is aimed at addressing the role of transcriptional complexity in the control of normal cell division and tumorigenesis using a systems wide approach. Rather than relying on the locus based study, this proposal seeks to take a systems biology approach, addressing the functional diversity of the expanded human phosphoregulator proteome, identifying all components of the network that are actively and dynamically expressed in the normal cell cycle and-or tumour progression, and then screening selected novel components for an ability regulate the cell cycle. Such studies will advance our understanding the involvements of the protein phosphorylation machinery in regulating cell division, highlight novel components potentially relevant tumorigenesis and potentially identify new chemotherapeutic targets.