Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing

Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x a...

Full description

Bibliographic Details
Authors: Montes, Marta, Coiras, Mayte, Becerra, Soraya, Moreno-Castro, Cristina, Mateos, Elena, Majuelos, Jara, Oliver, F Javier, Hernández-Munain, Cristina, Alcamí, José, Suñé, Carlos
Format: article
Publication Date:2015
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6910
Online Access:http://hdl.handle.net/20.500.12105/6910
Access Level:Open access
Keyword:Alternative Splicing
Apoptosis
Caspase 3
Cytochromes c
HEK293 Cells
HeLa Cells
Humans
Jurkat Cells
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Transcriptional Elongation Factors
bcl-2 Homologous Antagonist-Killer Protein
bcl-X Protein
fas Receptor
id ES_8d09ccc0f87cff97770cfadaa00433f8
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/6910
network_acronym_str ES
network_name_str España
repository_id_str
spelling Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative SplicingMontes, MartaCoiras, MayteBecerra, SorayaMoreno-Castro, CristinaMateos, ElenaMajuelos, JaraOliver, F JavierHernández-Munain, CristinaAlcamí, JoséSuñé, CarlosAlternative SplicingApoptosisCaspase 3Cytochromes cHEK293 CellsHeLa CellsHumansJurkat CellsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesTranscriptional Elongation Factorsbcl-2 Homologous Antagonist-Killer Proteinbcl-X Proteinfas ReceptorHere, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis.Public Library of Science (PLOS)Ministerio de Economía y Competitividad (España)Regional Government of Andalusia (España)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Ministerio de Educación (España)20182018-12-1920152015-10-1320152015-10-13journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/6910reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES BFU2011-24577 Not availableES BFU2014-54660-R Not availableES BFU2013-44660-R Not availableES SAF2013-44677-R Not availableES PI12 00506open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/69102026-06-12T12:43:37Z
dc.title.none.fl_str_mv Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
spellingShingle Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
Montes, Marta
Alternative Splicing
Apoptosis
Caspase 3
Cytochromes c
HEK293 Cells
HeLa Cells
Humans
Jurkat Cells
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Transcriptional Elongation Factors
bcl-2 Homologous Antagonist-Killer Protein
bcl-X Protein
fas Receptor
title_short Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_full Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_fullStr Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_full_unstemmed Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_sort Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
dc.creator.none.fl_str_mv Montes, Marta
Coiras, Mayte
Becerra, Soraya
Moreno-Castro, Cristina
Mateos, Elena
Majuelos, Jara
Oliver, F Javier
Hernández-Munain, Cristina
Alcamí, José
Suñé, Carlos
author Montes, Marta
author_facet Montes, Marta
Coiras, Mayte
Becerra, Soraya
Moreno-Castro, Cristina
Mateos, Elena
Majuelos, Jara
Oliver, F Javier
Hernández-Munain, Cristina
Alcamí, José
Suñé, Carlos
author_role author
author2 Coiras, Mayte
Becerra, Soraya
Moreno-Castro, Cristina
Mateos, Elena
Majuelos, Jara
Oliver, F Javier
Hernández-Munain, Cristina
Alcamí, José
Suñé, Carlos
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Regional Government of Andalusia (España)
Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Ministerio de Educación (España)
dc.subject.none.fl_str_mv Alternative Splicing
Apoptosis
Caspase 3
Cytochromes c
HEK293 Cells
HeLa Cells
Humans
Jurkat Cells
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Transcriptional Elongation Factors
bcl-2 Homologous Antagonist-Killer Protein
bcl-X Protein
fas Receptor
topic Alternative Splicing
Apoptosis
Caspase 3
Cytochromes c
HEK293 Cells
HeLa Cells
Humans
Jurkat Cells
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Transcriptional Elongation Factors
bcl-2 Homologous Antagonist-Killer Protein
bcl-X Protein
fas Receptor
description Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-10-13
2015
2015-10-13
2018
2018-12-19
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/6910
url http://hdl.handle.net/20.500.12105/6910
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES BFU2011-24577 Not available
ES BFU2014-54660-R Not available
ES BFU2013-44660-R Not available
ES SAF2013-44677-R Not available
ES PI12 00506
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLOS)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412997074518016
score 15.812429

Similar Items