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Identification and Functional Characterization of FMN2, a Regulator of the Cyclin-Dependent Kinase Inhibitor p21

Lookup NU author(s): Professor Neil PerkinsORCiD

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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-κB-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.

Publication metadata

Author(s): Yamada K, Ono M, Perkins ND, Rocha S, Lamond AI

Publication type: Article

Publication status: Published

Journal: Molecular Cell

Year: 2013

Volume: 49

Issue: 5

Pages: 922-933

Print publication date: 07/03/2013

Date deposited: 10/06/2013

ISSN (print): 1097-2765

ISSN (electronic): 1097-4164

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.molcel.2012.12.023

DOI: 10.1016/j.molcel.2012.12.023

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