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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...

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Autores principales: Zuchero, J. Bradley, Belin, Brittany, Mullins, R. Dyche
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
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.
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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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