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

Tsutomu Mori, Daisuke D. Ikeda, Yoshiki Yamaguchi, Motoko Unoki

    Research output: Contribution to journalReview articlepeer-review

    36 Citations (Scopus)


    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 "intermodular hub" 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's canals.

    Original languageEnglish
    Pages (from-to)1570-1583
    Number of pages14
    JournalFEBS Letters
    Issue number11
    Publication statusPublished - Jun 4 2012

    All Science Journal Classification (ASJC) codes

    • Biophysics
    • Structural Biology
    • Biochemistry
    • Molecular Biology
    • Genetics
    • Cell Biology


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