title: Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS, Granada, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Montes
authors.affiliation: AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Mayte
authors.initials: M
authors.lastname: Coiras
authors.affiliation: Department of Molecular Biology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS, Granada, Spain.
authors.forename: Soraya
authors.initials: S
authors.lastname: Becerra
authors.affiliation: Department of Molecular Biology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS, Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moreno-Castro
authors.affiliation: AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Mateos
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS, Granada, Spain.
authors.forename: Jara
authors.initials: J
authors.lastname: Majuelos
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS, Granada, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Oliver
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS, Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández-Munain
authors.affiliation: AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Alcamí
authors.affiliation: Department of Molecular Biology, Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS, Granada, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suñé
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: C494772:BAK1 protein, human; C494811:BCL2L1 protein, human; C491901:FAS protein, human; C108440:TCERG1 protein, human; D035602:Transcriptional Elongation Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; D019014:fas Receptor; D045304:Cytochromes c; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3