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.
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Authors | Kayo Yamada, Motoharu Ono, Neil D Perkins, Sonia Rocha, Angus I Lamond |
Journal | Molecular cell
(Mol Cell)
Vol. 49
Issue 5
Pg. 922-33
(Mar 07 2013)
ISSN: 1097-4164 [Electronic] United States |
PMID | 23375502
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- CDKN1A protein, human
- Cell Cycle Proteins
- Cyclin-Dependent Kinase Inhibitor p21
- NF-kappa B
- Nerve Tissue Proteins
- RNA, Messenger
- Tumor Suppressor Protein p14ARF
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Topics |
- Cell Cycle Checkpoints
- Cell Cycle Proteins
(genetics, metabolism)
- Cell Line, Tumor
- Cell Nucleolus
- Cyclin-Dependent Kinase Inhibitor p21
(genetics, metabolism)
- Humans
- Mass Spectrometry
- NF-kappa B
(genetics)
- Nerve Tissue Proteins
(genetics, metabolism)
- Proteomics
- RNA, Messenger
(metabolism)
- Tumor Suppressor Protein p14ARF
(genetics, metabolism)
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