title: CTS1: a p53-derived chimeric tumor suppressor gene with enhanced in vitro apoptotic properties.
abstract: The clinical potential of the p53 tumor suppressor gene is being evaluated currently for gene therapy of cancer. We have built a variant of wild-type p53, chimeric tumor suppressor 1 (CTS1), in which we have replaced the domains that mediate its inactivation. CTS1 presents some very interesting properties: (a) enhanced transcriptional activity; (b) resistance to the inactivation by oncogenic forms of p53; (c) resistance to the inactivation by MDM2; (d) lower sensitivity to E6-induced degradation; (e) ability to suppress cell growth; and (f ) faster induction of apoptosis. Thus, CTS1 is an improved tumor suppressor and an alternative for the treatment of wild-type p53-resistant human tumors by gene therapy.
authors.affiliation: Gene Medicine Department, Rhône-Poulenc Rorer SA, 94403 Vitry sur Seine Cedex, France.
authors.forename: E
authors.initials: E
authors.lastname: Conseiller
authors.forename: L
authors.initials: L
authors.lastname: Debussche
authors.forename: D
authors.initials: D
authors.lastname: Landais
authors.forename: C
authors.initials: C
authors.lastname: Venot
authors.forename: M
authors.initials: M
authors.lastname: Maratrat
authors.forename: V
authors.initials: V
authors.lastname: Sierra
authors.forename: B
authors.initials: B
authors.lastname: Tocque
authors.forename: L
authors.initials: L
authors.lastname: Bracco
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2