Foxo4 Transcriptional Activity is Regulated by Monoubiquitination and Usp7/Hausp.
From: Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Nature cell biology
- Publish Date: Oct 2006
- ISSN: 1465-7392
- Volume: 8
- Issue: 10
- Pages: 1064-73
- Medium: Print
- Language: English
- Citation (JAMA): van der Horst Armando, de Vries-Smits Alida M M, Brenkman Arjan B, et al. Foxo4 Transcriptional Activity is Regulated by Monoubiquitination and Usp7/Hausp.. Nat. Cell Biol. Oct 2006;8:1064-73
Abstract
FOXO (Forkhead box O) transcription factors are important regulators of cellular metabolism, cell-cycle progression and cell death. FOXO activity is regulated by multiple post-translational modifications, including phosphorylation, acetylation and polyubiquitination. Here, we show that FOXO becomes monoubiquitinated in response to increased cellular oxidative stress, resulting in its re-localization to the nucleus and an increase in its transcriptional activity. Deubiquitination of FOXO requires the deubiquitinating enzyme USP7/HAUSP (herpesvirus-associated ubiquitin-specific protease), which interacts with and deubiquitinates FOXO in response to oxidative stress. Oxidative stress-induced ubiquitination and deubiquitination by USP7 do not influence FOXO protein half-life. However, USP7 does negatively regulate FOXO transcriptional activity towards endogenous promoters. Our results demonstrate a novel mechanism of FOXO regulation and indicate that USP7 has an important role in regulating FOXO-mediated stress responses.
Mesh Headings (Keywords): Animals, Cells, Cultured, Endopeptidases, Gene Expression Regulation, Humans, Hydrogen Peroxide, Kidney, Lung Neoplasms, Mice, NIH 3T3 Cells, Oxidants, Oxidative Stress, Protein Processing, Post-Translational, RNA, Messenger, Transcription Factors, Transcription, Genetic, Transfection, Ubiquitin, Ubiquitin Thiolesterase
Check for Full Text / PubMed Unique Identifier (PMID): 16964248
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