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p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1
Chromosomal region maintenance 1 (CRM1) mediates p53 nuclear export. Although p53 SUMOylation promotes its nuclear export, the underlying mechanism is unclear. Here we show that tethering of a small, ubiquitin-like modifier (SUMO) moiety to p53 markedly increases its cytoplasmic localization. SUMO a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756925/ https://www.ncbi.nlm.nih.gov/pubmed/23825024 http://dx.doi.org/10.1091/mbc.E12-10-0771 |
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author | Santiago, Aleixo Li, Dawei Zhao, Lisa Y. Godsey, Adam Liao, Daiqing |
author_facet | Santiago, Aleixo Li, Dawei Zhao, Lisa Y. Godsey, Adam Liao, Daiqing |
author_sort | Santiago, Aleixo |
collection | PubMed |
description | Chromosomal region maintenance 1 (CRM1) mediates p53 nuclear export. Although p53 SUMOylation promotes its nuclear export, the underlying mechanism is unclear. Here we show that tethering of a small, ubiquitin-like modifier (SUMO) moiety to p53 markedly increases its cytoplasmic localization. SUMO attachment to p53 does not affect its oligomerization, suggesting that subunit dissociation required for exposing p53’s nuclear export signal (NES) is unnecessary for p53 nuclear export. Surprisingly, SUMO-mediated p53 nuclear export depends on the SUMO-interacting motif (SIM)-binding pocket of SUMO-1. The CRM1 C-terminal domain lacking the NES-binding groove interacts with tetrameric p53, and the proper folding of the p53 core domain, rather than the presence of the N- or C-terminal tails, appears to be important for p53–CRM1 interaction. The CRM1 Huntington, EF3, a subunit of PP2A, and TOR1 9 (HEAT9) loop, which regulates GTP-binding nuclear protein Ran binding and cargo release, contains a prototypical SIM. Remarkably, disruption of this SIM in conjunction with a mutated SIM-binding groove of SUMO-1 markedly enhances the binding of CRM1 to p53-SUMO-1 and their accumulation in the nuclear pore complexes (NPCs), as well as their persistent association in the cytoplasm. We propose that SUMOylation of a CRM1 cargo such as p53 at the NPCs unlocks the HEAT9 loop of CRM1 to facilitate the disassembly of the transporting complex and cargo release to the cytoplasm. |
format | Online Article Text |
id | pubmed-3756925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-37569252013-11-16 p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1 Santiago, Aleixo Li, Dawei Zhao, Lisa Y. Godsey, Adam Liao, Daiqing Mol Biol Cell Articles Chromosomal region maintenance 1 (CRM1) mediates p53 nuclear export. Although p53 SUMOylation promotes its nuclear export, the underlying mechanism is unclear. Here we show that tethering of a small, ubiquitin-like modifier (SUMO) moiety to p53 markedly increases its cytoplasmic localization. SUMO attachment to p53 does not affect its oligomerization, suggesting that subunit dissociation required for exposing p53’s nuclear export signal (NES) is unnecessary for p53 nuclear export. Surprisingly, SUMO-mediated p53 nuclear export depends on the SUMO-interacting motif (SIM)-binding pocket of SUMO-1. The CRM1 C-terminal domain lacking the NES-binding groove interacts with tetrameric p53, and the proper folding of the p53 core domain, rather than the presence of the N- or C-terminal tails, appears to be important for p53–CRM1 interaction. The CRM1 Huntington, EF3, a subunit of PP2A, and TOR1 9 (HEAT9) loop, which regulates GTP-binding nuclear protein Ran binding and cargo release, contains a prototypical SIM. Remarkably, disruption of this SIM in conjunction with a mutated SIM-binding groove of SUMO-1 markedly enhances the binding of CRM1 to p53-SUMO-1 and their accumulation in the nuclear pore complexes (NPCs), as well as their persistent association in the cytoplasm. We propose that SUMOylation of a CRM1 cargo such as p53 at the NPCs unlocks the HEAT9 loop of CRM1 to facilitate the disassembly of the transporting complex and cargo release to the cytoplasm. The American Society for Cell Biology 2013-09-01 /pmc/articles/PMC3756925/ /pubmed/23825024 http://dx.doi.org/10.1091/mbc.E12-10-0771 Text en © 2013 Santiago 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 Santiago, Aleixo Li, Dawei Zhao, Lisa Y. Godsey, Adam Liao, Daiqing p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1 |
title | p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1 |
title_full | p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1 |
title_fullStr | p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1 |
title_full_unstemmed | p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1 |
title_short | p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1 |
title_sort | p53 sumoylation promotes its nuclear export by facilitating its release from the nuclear export receptor crm1 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756925/ https://www.ncbi.nlm.nih.gov/pubmed/23825024 http://dx.doi.org/10.1091/mbc.E12-10-0771 |
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