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Title: The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

Abstract

Highlights: •Sodium arsenite induces cytoplasmic accumulation of Id3. •Arsenite binds to closely spaced N-terminal cysteine residues of Id3. •N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. •Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines.more » Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite.« less

Authors:
 [1];  [2];  [1];  [1]
  1. Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)
  2. Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto (Japan)
Publication Date:
OSTI Identifier:
22239553
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 433; Journal Issue: 4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARSENIC; CELL PROLIFERATION; CYSTEINE; CYTOPLASM; MUTATIONS; OXIDES; PHOSPHOTRANSFERASES; RESIDUES; SIGNALS; TRANSCRIPTION

Citation Formats

Kurooka, Hisanori, Research and Education Program for Life Science, University of Fukui, Fukui, Sugai, Manabu, Mori, Kentaro, Yokota, Yoshifumi, and Research and Education Program for Life Science, University of Fukui, Fukui. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.03.027.
Kurooka, Hisanori, Research and Education Program for Life Science, University of Fukui, Fukui, Sugai, Manabu, Mori, Kentaro, Yokota, Yoshifumi, & Research and Education Program for Life Science, University of Fukui, Fukui. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues. United States. https://doi.org/10.1016/J.BBRC.2013.03.027
Kurooka, Hisanori, Research and Education Program for Life Science, University of Fukui, Fukui, Sugai, Manabu, Mori, Kentaro, Yokota, Yoshifumi, and Research and Education Program for Life Science, University of Fukui, Fukui. 2013. "The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues". United States. https://doi.org/10.1016/J.BBRC.2013.03.027.
@article{osti_22239553,
title = {The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues},
author = {Kurooka, Hisanori and Research and Education Program for Life Science, University of Fukui, Fukui and Sugai, Manabu and Mori, Kentaro and Yokota, Yoshifumi and Research and Education Program for Life Science, University of Fukui, Fukui},
abstractNote = {Highlights: •Sodium arsenite induces cytoplasmic accumulation of Id3. •Arsenite binds to closely spaced N-terminal cysteine residues of Id3. •N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. •Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite.},
doi = {10.1016/J.BBRC.2013.03.027},
url = {https://www.osti.gov/biblio/22239553}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 433,
place = {United States},
year = {Fri Apr 19 00:00:00 EDT 2013},
month = {Fri Apr 19 00:00:00 EDT 2013}
}