title: CSB ablation induced apoptosis is mediated by increased endoplasmic reticulum stress response.
abstract: The DNA repair protein Cockayne syndrome group B (CSB) has been recently identified as a promising anticancer target. Suppression, by antisense technology, of this protein causes devastating effects on tumor cells viability, through a massive induction of apoptosis, while being non-toxic to non-transformed cells. To gain insights into the mechanisms underlying the pro-apoptotic effects observed after CSB ablation, global gene expression patterns were determined, to identify genes that were significantly differentially regulated as a function of CSB expression. Our findings revealed that response to endoplasmic reticulum stress and response to unfolded proteins were ranked top amongst the cellular processes affected by CSB suppression. The major components of the endoplasmic reticulum stress-mediated apoptosis pathway, including pro-apoptotic factors downstream of the ATF3-CHOP cascade, were dramatically up-regulated. Altogether our findings add new pieces to the understanding of CSB mechanisms of action and to the molecular basis of CS syndrome.
authors.affiliation: Unit of Molecular Genetics of Aging-Department of Ecology and Biology-University of Tuscia, Viterbo, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Caputo
authors.affiliation: Unit of Molecular Genetics of Aging-Department of Ecology and Biology-University of Tuscia, Viterbo, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Balzerano
authors.affiliation: Genomics Facility, European Brain Research Institute (EBRI) "Rita Levi-Montalcini", Rome, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Arisi
authors.affiliation: Genomics Facility, European Brain Research Institute (EBRI) "Rita Levi-Montalcini", Rome, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: D'Onofrio
authors.affiliation: Genomics Facility, European Brain Research Institute (EBRI) "Rita Levi-Montalcini", Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Brandi
authors.affiliation: Unit of Molecular Genetics of Aging-Department of Ecology and Biology-University of Tuscia, Viterbo, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bongiorni
authors.affiliation: Department of Experimental Medicine-Section of Terni, University of Perugia, Terni, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Brancorsini
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.|National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.|British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Mattia
authors.initials: M
authors.lastname: Frontini
authors.affiliation: Unit of Molecular Genetics of Aging-Department of Ecology and Biology-University of Tuscia, Viterbo, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Proietti-De-Santis
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D004265:DNA Helicases / Q000172:deficiency* / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000172:deficiency* / Q000235:genetics*; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes