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质磷酸化的细胞机制的基因。在哺乳动物中，激酶和磷酸酶分子网络的大小比以前报道的要复杂得多，许多激酶和磷酸酶基因座平均每个基因产生4个以上的转录本。这项资助的目的是解决转录复杂性在控制正常细胞分裂和肿瘤发生中的作用，使用系统范围的方法。这项建议不依赖于基于位点的研究，而是寻求采用系统生物学的方法，解决扩展的人类磷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，然后筛选出调节细胞周期的能力的选定的新组件。这些研究将促进我们对蛋白质磷酸化机制在调节细胞分裂中的参与的理解，突出新的成分，潜在地与肿瘤发生相关，并可能识别新的化疗靶点。

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.