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BTK modulates p73 activity to induce apoptosis independently of p53
Bruton’s tyrosine kinase (BTK) is a key component of B cell receptor signalling. Because of this, BTK plays an important role in cell proliferation and survival in various B cell malignancies. However, in certain contexts, BTK can also have tumour suppressor functions. We have previously shown that...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134113/ https://www.ncbi.nlm.nih.gov/pubmed/30245853 http://dx.doi.org/10.1038/s41420-018-0097-7 |
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author | Rada, Miran Barlev, Nickolai Macip, Salvador |
author_facet | Rada, Miran Barlev, Nickolai Macip, Salvador |
author_sort | Rada, Miran |
collection | PubMed |
description | Bruton’s tyrosine kinase (BTK) is a key component of B cell receptor signalling. Because of this, BTK plays an important role in cell proliferation and survival in various B cell malignancies. However, in certain contexts, BTK can also have tumour suppressor functions. We have previously shown that BTK activates the p53 transcriptional activity by binding to and phosphorylating p53, as well as acting on MDM2 to reduce its inhibitory effects. This results in increased p53 functions, including enhanced cell death. Here, we report that BTK can also induce cell death and increase responses to DNA damage independently of p53. This is concomitant to the induction of p21, PUMA and MDM2, which are classic target genes of the p53 family of proteins. Our results show that these p53-independent effects of BTK are mediated through p73. Similar to what we observed in the p53 pathway, BTK can upregulate p73 after DNA damage and induce expression of its target genes, suggesting that BTK is a modulator of p73 functions and in the absence of p53. This effect allows BTK to have pro-apoptotic functions independently of its effects on the p53 pathway and thus play an important role in the DNA damage-related induction of apoptosis in the absence of p53. This provides a novel role of BTK in tumour suppression and contributes to the understanding of its complex pleiotropic functions |
format | Online Article Text |
id | pubmed-6134113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61341132018-09-21 BTK modulates p73 activity to induce apoptosis independently of p53 Rada, Miran Barlev, Nickolai Macip, Salvador Cell Death Discov Article Bruton’s tyrosine kinase (BTK) is a key component of B cell receptor signalling. Because of this, BTK plays an important role in cell proliferation and survival in various B cell malignancies. However, in certain contexts, BTK can also have tumour suppressor functions. We have previously shown that BTK activates the p53 transcriptional activity by binding to and phosphorylating p53, as well as acting on MDM2 to reduce its inhibitory effects. This results in increased p53 functions, including enhanced cell death. Here, we report that BTK can also induce cell death and increase responses to DNA damage independently of p53. This is concomitant to the induction of p21, PUMA and MDM2, which are classic target genes of the p53 family of proteins. Our results show that these p53-independent effects of BTK are mediated through p73. Similar to what we observed in the p53 pathway, BTK can upregulate p73 after DNA damage and induce expression of its target genes, suggesting that BTK is a modulator of p73 functions and in the absence of p53. This effect allows BTK to have pro-apoptotic functions independently of its effects on the p53 pathway and thus play an important role in the DNA damage-related induction of apoptosis in the absence of p53. This provides a novel role of BTK in tumour suppression and contributes to the understanding of its complex pleiotropic functions Nature Publishing Group UK 2018-09-11 /pmc/articles/PMC6134113/ /pubmed/30245853 http://dx.doi.org/10.1038/s41420-018-0097-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Rada, Miran Barlev, Nickolai Macip, Salvador BTK modulates p73 activity to induce apoptosis independently of p53 |
title | BTK modulates p73 activity to induce apoptosis independently of p53 |
title_full | BTK modulates p73 activity to induce apoptosis independently of p53 |
title_fullStr | BTK modulates p73 activity to induce apoptosis independently of p53 |
title_full_unstemmed | BTK modulates p73 activity to induce apoptosis independently of p53 |
title_short | BTK modulates p73 activity to induce apoptosis independently of p53 |
title_sort | btk modulates p73 activity to induce apoptosis independently of p53 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134113/ https://www.ncbi.nlm.nih.gov/pubmed/30245853 http://dx.doi.org/10.1038/s41420-018-0097-7 |
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