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Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor
BACKGROUND: Breast cancer metastasis suppressor 1 (BRMS1) reduces the number and the size of secondary tumours in a mouse model without affecting the growth of the primary foci upon its re-expression. Knockdown of BRMS1 expression associates with metastasis. The molecular details on BRMS1 mechanism...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713406/ https://www.ncbi.nlm.nih.gov/pubmed/19649328 http://dx.doi.org/10.1371/journal.pone.0006433 |
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author | Rivera, José Megías, Diego Navas, Carolina Bravo, Jerónimo |
author_facet | Rivera, José Megías, Diego Navas, Carolina Bravo, Jerónimo |
author_sort | Rivera, José |
collection | PubMed |
description | BACKGROUND: Breast cancer metastasis suppressor 1 (BRMS1) reduces the number and the size of secondary tumours in a mouse model without affecting the growth of the primary foci upon its re-expression. Knockdown of BRMS1 expression associates with metastasis. The molecular details on BRMS1 mechanism of action include its ability to function as a transcriptional co-repressor and consistently BRMS1 has been described as a predominantly nuclear protein. Since cellular distribution could represent a potential mechanism of regulation, we wanted to characterize BRMS1 sequence motifs that might regulate its cellular distribution. According to its amino acids sequence, BRMS1 contain two putative nuclear localization signals, however none of them has been proved to work so far. METHODOLOGY/PRINCIPAL FINDINGS: By using well known in vivo assays to detect both nuclear import and export signal, we have characterized, in the present study, one functional nuclear localisation signal as necessary and sufficient to promote nuclear transport. Additionally, the outcome of a directed yeast two-hybrid assay identify importin α6 as a specific partner of BRMS1 thus speculating that BRMS1 nuclear import could be specifically mediated by the reported nuclear transporter. Besides, the combination of a computational searching approach along the utilization of a nuclear export assay, identified a functional motif within the BRMS1 sequence responsible for its nuclear export, that resulted not affected by the highly specific CRM1 inhibitor Leptomycin-B. Interspecies heterokaryon assay demonstrate the capability of BRMS1 to shuttle between the nuclear and cytosolic compartments CONCLUSIONS/SIGNIFICANCE: Our results show for the first time that BRMS1 contains both nuclear import and export signals enabling its nucleo-cytoplasmic shuttling. These findings contributes new data for the understanding of the BRMS1 functions and allow us to speculate that this phenomenon could represent a novel mechanism for regulating the activity of BRMS1 or its associated cytosolic partners |
format | Text |
id | pubmed-2713406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27134062009-08-01 Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor Rivera, José Megías, Diego Navas, Carolina Bravo, Jerónimo PLoS One Research Article BACKGROUND: Breast cancer metastasis suppressor 1 (BRMS1) reduces the number and the size of secondary tumours in a mouse model without affecting the growth of the primary foci upon its re-expression. Knockdown of BRMS1 expression associates with metastasis. The molecular details on BRMS1 mechanism of action include its ability to function as a transcriptional co-repressor and consistently BRMS1 has been described as a predominantly nuclear protein. Since cellular distribution could represent a potential mechanism of regulation, we wanted to characterize BRMS1 sequence motifs that might regulate its cellular distribution. According to its amino acids sequence, BRMS1 contain two putative nuclear localization signals, however none of them has been proved to work so far. METHODOLOGY/PRINCIPAL FINDINGS: By using well known in vivo assays to detect both nuclear import and export signal, we have characterized, in the present study, one functional nuclear localisation signal as necessary and sufficient to promote nuclear transport. Additionally, the outcome of a directed yeast two-hybrid assay identify importin α6 as a specific partner of BRMS1 thus speculating that BRMS1 nuclear import could be specifically mediated by the reported nuclear transporter. Besides, the combination of a computational searching approach along the utilization of a nuclear export assay, identified a functional motif within the BRMS1 sequence responsible for its nuclear export, that resulted not affected by the highly specific CRM1 inhibitor Leptomycin-B. Interspecies heterokaryon assay demonstrate the capability of BRMS1 to shuttle between the nuclear and cytosolic compartments CONCLUSIONS/SIGNIFICANCE: Our results show for the first time that BRMS1 contains both nuclear import and export signals enabling its nucleo-cytoplasmic shuttling. These findings contributes new data for the understanding of the BRMS1 functions and allow us to speculate that this phenomenon could represent a novel mechanism for regulating the activity of BRMS1 or its associated cytosolic partners Public Library of Science 2009-07-30 /pmc/articles/PMC2713406/ /pubmed/19649328 http://dx.doi.org/10.1371/journal.pone.0006433 Text en Rivera et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rivera, José Megías, Diego Navas, Carolina Bravo, Jerónimo Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor |
title | Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor |
title_full | Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor |
title_fullStr | Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor |
title_full_unstemmed | Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor |
title_short | Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor |
title_sort | identification of essential sequences for cellular localization in brms1 metastasis suppressor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713406/ https://www.ncbi.nlm.nih.gov/pubmed/19649328 http://dx.doi.org/10.1371/journal.pone.0006433 |
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