Identification and functional characterization of FMN2: a regulator of the cyclin-dependent kinase Inhibitor p21

Kayo Yamada, Motoharu Ono, Neil D. Perkins, Sonia Rocha (Lead / Corresponding author), Angus I. Lamond (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)

    Abstract

    The ARF tumor suppressor is a central component of the cellular defense against oncogene activation in mammals. p14ARF activates p53 by binding and inhibiting HDM2, resulting, inter alia, in increased transcription and expression of the cyclin-dependent kinase inhibitor p21 and consequent cell-cycle arrest. We analyzed the effect of p14ARF induction on nucleolar protein dynamics using SILAC mass spectrometry and have identified the human Formin-2 (FMN2) protein as a component of the p14ARF tumor suppressor pathway. We show that FMN2 is increased upon p14ARF induction at both the mRNA and the protein level via a NF-?B-dependent mechanism that is independent of p53. FMN2 enhances expression of the cell-cycle inhibitor p21 by preventing its degradation. FMN2 is also induced by activation of other oncogenes, hypoxia, and DNA damage. These results identify FMN2 as a crucial component in the regulation of p21 and consequent oncogene/stress-induced cell-cycle arrest in human cells.
    Original languageEnglish
    Pages (from-to)922-933
    Number of pages12
    JournalMolecular Cell
    Volume49
    Issue number5
    DOIs
    Publication statusPublished - Mar 2013

    Fingerprint Dive into the research topics of 'Identification and functional characterization of FMN2: a regulator of the cyclin-dependent kinase Inhibitor p21'. Together they form a unique fingerprint.

    Cite this