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14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport
14-3-3 proteins regulate the cell cycle and prevent apoptosis by controlling the nuclear and cytoplasmic distribution of signaling molecules with which they interact. Although the majority of 14-3-3 molecules are present in the cytoplasm, we show here that in the absence of bound ligands 14-3-3 home...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173313/ https://www.ncbi.nlm.nih.gov/pubmed/11864996 http://dx.doi.org/10.1083/jcb.200112059 |
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author | Brunet, Anne Kanai, Fumihiko Stehn, Justine Xu, Jian Sarbassova, Dilara Frangioni, John V. Dalal, Sorab N. DeCaprio, James A. Greenberg, Michael E. Yaffe, Michael B. |
author_facet | Brunet, Anne Kanai, Fumihiko Stehn, Justine Xu, Jian Sarbassova, Dilara Frangioni, John V. Dalal, Sorab N. DeCaprio, James A. Greenberg, Michael E. Yaffe, Michael B. |
author_sort | Brunet, Anne |
collection | PubMed |
description | 14-3-3 proteins regulate the cell cycle and prevent apoptosis by controlling the nuclear and cytoplasmic distribution of signaling molecules with which they interact. Although the majority of 14-3-3 molecules are present in the cytoplasm, we show here that in the absence of bound ligands 14-3-3 homes to the nucleus. We demonstrate that phosphorylation of one important 14-3-3 binding molecule, the transcription factor FKHRL1, at the 14-3-3 binding site occurs within the nucleus immediately before FKHRL1 relocalization to the cytoplasm. We show that the leucine-rich region within the COOH-terminal α-helix of 14-3-3, which had been proposed to function as a nuclear export signal (NES), instead functions globally in ligand binding and does not directly mediate nuclear transport. Efficient nuclear export of FKHRL1 requires both intrinsic NES sequences within FKHRL1 and phosphorylation/14-3-3 binding. Finally, we present evidence that phosphorylation/14-3-3 binding may also prevent FKHRL1 nuclear reimport. These results indicate that 14-3-3 can mediate the relocalization of nuclear ligands by several mechanisms that ensure complete sequestration of the bound 14-3-3 complex in the cytoplasm. |
format | Text |
id | pubmed-2173313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21733132008-05-01 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport Brunet, Anne Kanai, Fumihiko Stehn, Justine Xu, Jian Sarbassova, Dilara Frangioni, John V. Dalal, Sorab N. DeCaprio, James A. Greenberg, Michael E. Yaffe, Michael B. J Cell Biol Article 14-3-3 proteins regulate the cell cycle and prevent apoptosis by controlling the nuclear and cytoplasmic distribution of signaling molecules with which they interact. Although the majority of 14-3-3 molecules are present in the cytoplasm, we show here that in the absence of bound ligands 14-3-3 homes to the nucleus. We demonstrate that phosphorylation of one important 14-3-3 binding molecule, the transcription factor FKHRL1, at the 14-3-3 binding site occurs within the nucleus immediately before FKHRL1 relocalization to the cytoplasm. We show that the leucine-rich region within the COOH-terminal α-helix of 14-3-3, which had been proposed to function as a nuclear export signal (NES), instead functions globally in ligand binding and does not directly mediate nuclear transport. Efficient nuclear export of FKHRL1 requires both intrinsic NES sequences within FKHRL1 and phosphorylation/14-3-3 binding. Finally, we present evidence that phosphorylation/14-3-3 binding may also prevent FKHRL1 nuclear reimport. These results indicate that 14-3-3 can mediate the relocalization of nuclear ligands by several mechanisms that ensure complete sequestration of the bound 14-3-3 complex in the cytoplasm. The Rockefeller University Press 2002-03-04 /pmc/articles/PMC2173313/ /pubmed/11864996 http://dx.doi.org/10.1083/jcb.200112059 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Brunet, Anne Kanai, Fumihiko Stehn, Justine Xu, Jian Sarbassova, Dilara Frangioni, John V. Dalal, Sorab N. DeCaprio, James A. Greenberg, Michael E. Yaffe, Michael B. 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport |
title | 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport |
title_full | 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport |
title_fullStr | 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport |
title_full_unstemmed | 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport |
title_short | 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport |
title_sort | 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173313/ https://www.ncbi.nlm.nih.gov/pubmed/11864996 http://dx.doi.org/10.1083/jcb.200112059 |
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