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Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY
Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Al...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290644/ https://www.ncbi.nlm.nih.gov/pubmed/22262458 http://dx.doi.org/10.1091/mbc.E11-12-0992 |
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author | Zuchero, J. Bradley Belin, Brittany Mullins, R. Dyche |
author_facet | Zuchero, J. Bradley Belin, Brittany Mullins, R. Dyche |
author_sort | Zuchero, J. Bradley |
collection | PubMed |
description | Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage. |
format | Online Article Text |
id | pubmed-3290644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32906442012-05-16 Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY Zuchero, J. Bradley Belin, Brittany Mullins, R. Dyche Mol Biol Cell Articles Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage. The American Society for Cell Biology 2012-03-01 /pmc/articles/PMC3290644/ /pubmed/22262458 http://dx.doi.org/10.1091/mbc.E11-12-0992 Text en © 2012 Zuchero et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Zuchero, J. Bradley Belin, Brittany Mullins, R. Dyche Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY |
title | Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY |
title_full | Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY |
title_fullStr | Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY |
title_full_unstemmed | Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY |
title_short | Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY |
title_sort | actin binding to wh2 domains regulates nuclear import of the multifunctional actin regulator jmy |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290644/ https://www.ncbi.nlm.nih.gov/pubmed/22262458 http://dx.doi.org/10.1091/mbc.E11-12-0992 |
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