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...

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Detalles Bibliográficos
Autores: Montes-Resano, M. (Marta)|||/items/a4f2bd35-a15c-47ff-a3db-2ca1c35dcdde, Coiras, M. (Mayte)|||/items/ec5805c6-dbf9-481f-9746-e62ed483cf29, Becerra, S. (Soraya)|||/items/231c8d73-1dd9-4c1c-bba8-208aa15c874f, Moreno-Castro, C. (Cristina)|||/items/a57573ee-0602-452a-b549-5331b6c919af, Mateos, E. (Elena)|||/items/78ee8e4d-2c8e-4bdb-b5cc-8899b20b9392, Majuelos, J. (Jara)|||/items/45f3ff02-20fb-49e6-ae59-e2b0360ceb3c, Oliver, F.J. (F. Javier)|||/items/095cbbd2-89b7-4779-b5c7-085b2d6a1443, Hernández-Munain, C. (Cristina)|||/items/ae745215-fad3-4634-88e8-3f9d93cac55d, Alcamí, J. (José)|||/items/c59b8983-2253-45fc-ae7a-6af003e451d2, Suñé, C. (Carlos)|||/items/9bf75fc3-8467-479d-b9b4-33567f57b89d
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/122001
Acceso en línea:https://hdl.handle.net/10171/122001
Access Level:acceso abierto
Palabra clave:Apoptosis
TCERG1
Descripción
Sumario: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.

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