title: Cloning and functional characterization of the murine caspase-3 gene promoter.
abstract: Several studies have shown that the levels of caspase-3 are upregulated under different conditions of apoptosis. Previously, we have shown that activation of T cells through the TCR leads to the upregulation of caspase-3 levels. These findings highlight the importance of regulating the expression of caspase-3 in order to prevent premature cell death. To better understand the regulation of the caspase-3 gene, a portion of the 5'- untranslated region was cloned, sequenced, and characterized. The segment of the 5'-flanking region of the caspase-3 gene was also cloned upstream of a luciferase reporter gene, demonstrating that this fragment contains promoter activity. Higher luciferase expression was found with several of the promoter deletion constructs in Jurkat T cells but not the mouse Neuro-2A neuroblastoma cell line, suggesting the presence of a T-cell-specific regulated region. The importance of these sequences is further supported by the genomic organization of the human and mouse caspase-3 promoter regions. These findings demonstrated that the -2245/+14 region of the caspase-3 promoter shows constitutive levels of expression, and that several regions of the promoter play a role in basal regulation. Finally, some of the conserved transcription factor binding sites identified between the human and mouse promoters appear to play an important role in lymphoid cells.
authors.affiliation: Laboratoire d'Immunologie, Centre de Recherche du CHUM, Campus St.-Luc, Pavillon Edouard-Asselin, 264 Boulevard René Lévesque Est, #1370D, Montreal, Quebec H3C 3J7, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Sabbagh
authors.forename: Martin
authors.initials: M
authors.lastname: Bourbonnière
authors.forename: François
authors.initials: F
authors.lastname: Denis
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000235:genetics*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic
chemical_list: D020121:5' Untranslated Regions; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases