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MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study

BACKGROUND AND PURPOSE: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38β), MAPK12 (p38γ) and MAPK13 (p38δ)....

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Autores principales: Fernández-Aroca, D.M., García-Flores, N., Frost, S., Jiménez-Suárez, J., Rodríguez-González, A., Fernández-Aroca, P., Sabater, S., Andrés, I., Garnés-García, C., Belandia, B., Cimas, F.J., Villar, D., Ruiz-Hidalgo, M.J., Sánchez-Prieto, R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279794/
https://www.ncbi.nlm.nih.gov/pubmed/37346275
http://dx.doi.org/10.1016/j.ctro.2023.100649
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author Fernández-Aroca, D.M.
García-Flores, N.
Frost, S.
Jiménez-Suárez, J.
Rodríguez-González, A.
Fernández-Aroca, P.
Sabater, S.
Andrés, I.
Garnés-García, C.
Belandia, B.
Cimas, F.J.
Villar, D.
Ruiz-Hidalgo, M.J.
Sánchez-Prieto, R.
author_facet Fernández-Aroca, D.M.
García-Flores, N.
Frost, S.
Jiménez-Suárez, J.
Rodríguez-González, A.
Fernández-Aroca, P.
Sabater, S.
Andrés, I.
Garnés-García, C.
Belandia, B.
Cimas, F.J.
Villar, D.
Ruiz-Hidalgo, M.J.
Sánchez-Prieto, R.
author_sort Fernández-Aroca, D.M.
collection PubMed
description BACKGROUND AND PURPOSE: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38β), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR). MATERIALS AND METHODS: We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR. RESULTS: Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair. CONCLUSION: Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence.
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spelling pubmed-102797942023-06-21 MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study Fernández-Aroca, D.M. García-Flores, N. Frost, S. Jiménez-Suárez, J. Rodríguez-González, A. Fernández-Aroca, P. Sabater, S. Andrés, I. Garnés-García, C. Belandia, B. Cimas, F.J. Villar, D. Ruiz-Hidalgo, M.J. Sánchez-Prieto, R. Clin Transl Radiat Oncol Original Research Article BACKGROUND AND PURPOSE: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38β), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR). MATERIALS AND METHODS: We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR. RESULTS: Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair. CONCLUSION: Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence. Elsevier 2023-06-02 /pmc/articles/PMC10279794/ /pubmed/37346275 http://dx.doi.org/10.1016/j.ctro.2023.100649 Text en © 2023 The Author(s) https://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 Original Research Article
Fernández-Aroca, D.M.
García-Flores, N.
Frost, S.
Jiménez-Suárez, J.
Rodríguez-González, A.
Fernández-Aroca, P.
Sabater, S.
Andrés, I.
Garnés-García, C.
Belandia, B.
Cimas, F.J.
Villar, D.
Ruiz-Hidalgo, M.J.
Sánchez-Prieto, R.
MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study
title MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study
title_full MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study
title_fullStr MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study
title_full_unstemmed MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study
title_short MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study
title_sort mapk11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: an in vitro study
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279794/
https://www.ncbi.nlm.nih.gov/pubmed/37346275
http://dx.doi.org/10.1016/j.ctro.2023.100649
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