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

TY - JOUR

T1 - Identification and functional characterization of FMN2

T2 - a regulator of the cyclin-dependent kinase Inhibitor p21

AU - Yamada, Kayo

AU - Ono, Motoharu

AU - Perkins, Neil D.

AU - Rocha, Sonia

AU - Lamond, Angus I.

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84876864559

U2 - 10.1016/j.molcel.2012.12.023

DO - 10.1016/j.molcel.2012.12.023

M3 - Article

C2 - 23375502

SN - 1097-4164

VL - 49

SP - 922

EP - 933

JO - Molecular Cell

JF - Molecular Cell

IS - 5

ER -