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Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region
BCL-2-related ovarian killer (BOK) is a pro-apoptotic BAX-like member of the BCL-2 family with suggested tumor suppressor activity. The molecular mechanisms regulating BOK expression are poorly understood and fail to explain a frequent lack of concordance between protein and transcript levels. Here,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260365/ https://www.ncbi.nlm.nih.gov/pubmed/30471638 http://dx.doi.org/10.1016/j.isci.2018.11.005 |
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author | Fernandez-Marrero, Yuniel Bachmann, Daniel Lauber, Emanuel Kaufmann, Thomas |
author_facet | Fernandez-Marrero, Yuniel Bachmann, Daniel Lauber, Emanuel Kaufmann, Thomas |
author_sort | Fernandez-Marrero, Yuniel |
collection | PubMed |
description | BCL-2-related ovarian killer (BOK) is a pro-apoptotic BAX-like member of the BCL-2 family with suggested tumor suppressor activity. The molecular mechanisms regulating BOK expression are poorly understood and fail to explain a frequent lack of concordance between protein and transcript levels. Here, we describe a potent post-transcriptional mechanism that negatively regulates BOK expression mediated by conserved (AU/U)-rich elements within its 3’ UTR. Using proteomics approaches we identified TRIM28 as a key component associating with U-rich elements in the human BOK 3’ UTR, resulting in a dramatic reduction of BOK expression. TRIM28 is overexpressed in several cancers, correlating with poor patient outcome, whereas the BOK locus is frequently deleted or its expression downregulated in human cancers. Data mining indicated that, for certain cancers, high TRIM28 and low BOK expression are significantly correlated in the stratum of patients with the worst survival, suggesting that this mechanism might be of potential therapeutic value. |
format | Online Article Text |
id | pubmed-6260365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-62603652018-12-05 Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region Fernandez-Marrero, Yuniel Bachmann, Daniel Lauber, Emanuel Kaufmann, Thomas iScience Article BCL-2-related ovarian killer (BOK) is a pro-apoptotic BAX-like member of the BCL-2 family with suggested tumor suppressor activity. The molecular mechanisms regulating BOK expression are poorly understood and fail to explain a frequent lack of concordance between protein and transcript levels. Here, we describe a potent post-transcriptional mechanism that negatively regulates BOK expression mediated by conserved (AU/U)-rich elements within its 3’ UTR. Using proteomics approaches we identified TRIM28 as a key component associating with U-rich elements in the human BOK 3’ UTR, resulting in a dramatic reduction of BOK expression. TRIM28 is overexpressed in several cancers, correlating with poor patient outcome, whereas the BOK locus is frequently deleted or its expression downregulated in human cancers. Data mining indicated that, for certain cancers, high TRIM28 and low BOK expression are significantly correlated in the stratum of patients with the worst survival, suggesting that this mechanism might be of potential therapeutic value. Elsevier 2018-11-10 /pmc/articles/PMC6260365/ /pubmed/30471638 http://dx.doi.org/10.1016/j.isci.2018.11.005 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Fernandez-Marrero, Yuniel Bachmann, Daniel Lauber, Emanuel Kaufmann, Thomas Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region |
title | Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region |
title_full | Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region |
title_fullStr | Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region |
title_full_unstemmed | Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region |
title_short | Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region |
title_sort | negative regulation of bok expression by recruitment of trim28 to regulatory elements in its 3′ untranslated region |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260365/ https://www.ncbi.nlm.nih.gov/pubmed/30471638 http://dx.doi.org/10.1016/j.isci.2018.11.005 |
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