NIRF/UHRF2 occupies a central position in the cell cycle network and allows coupling with the epigenetic landscape

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• 作者：Tsutomu Mori^a ; ¹ ; ^{tmori@fmu.ac.jp} ; Daisuke D. Ikeda^b ; ¹ ; Yoshiki Yamaguchi^c ; ¹ ; Motoko Unoki^d ; ¹ ; NIRF Project¹
• 关键词：CAN gene ; candidate cancer gene ; CD ; cluster of differentiation ; CDK ; cyclin-dependent kinase ; COPA ; cancer outlier profile analysis ; DNMT ; DNA methyltransferase ; GRN ; gene regulatory network ; HDAC ; histone deacetylase ; H3K9 ; Histone H3 lysine 9 ; ICBP90
• 刊名：FEBS Letters
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：4 June, 2012
• 卷：586
• 期：11
• 页码：1570-1583
• 文件大小：1305 K

摘要

As predicted by systems biology, a paradigm shift will emerge through the integration of information about different layers of cellular processes. The cell cycle network is at the heart of the cellular computing system, and orchestrates versatile cellular functions. The NIRF/UHRF2 ubiquitin ligase is an 鈥渋ntermodular hub鈥?that occupies a central position in the network, and facilitates coordination among the cell cycle machinery, the ubiquitin-proteasome system, and the epigenetic system. NIRF interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. NIRF ubiquitinates cyclins D1 and E1, and induces G1 arrest. The NIRF gene is frequently lost in tumors and is a candidate tumor suppressor, while its paralog, the UHRF1 gene, is hardly altered. Thus, investigations of NIRF are essential to understand the entire biological systems. Through integration of the enormous information flows, NIRF may contribute to the coupling between the cell cycle network and the epigenetic landscape. We propose the new paradigm that NIRF produces the extreme diversity in the network wiring that helps the diversity of Waddington鈥檚 canals.