title: P53-dependent expression of the stress-induced protein (SIP).
abstract: The mouse stress-induced protein (SIP) mRNA is activated in the pancreas with acute pancreatitis and in several cell lines in response to various stress agents. The SIP gene is alternatively spliced, generating two proteins (SIP'8 and SIP27). Both proteins, located mainly in the nucleus, promote cell death when overexpressed in vitro. We show that induction by stress agents of the expression of SIP18 and SIP27 mRNAs, observed in human- and mouse-derived cell lines, is absent from cells with deleted, mutated or inactive p53, suggesting that regulation of SIP gene expression is dependent on p53. That hypothesis is consistent with the presence of a functional p53-response element within the promoter region of the mouse SIP gene and confirmed by the induction of SIP mRNA expression in mouse embryo fibroblasts upon activation of a p53-dependent pathway by transfection with rasV12 or rasV12/E1A. In conclusion, SIP being a proapoptotic gene induced through p53 activation could be a stress-induced gene with antitumour properties.
authors.affiliation: Centre de Recherche INSERM, EMI 0116, Marseille, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Tomasini
authors.forename: Amina Azizi
authors.initials: AA
authors.lastname: Samir
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Pebusque
authors.forename: Ezequiel L
authors.initials: EL
authors.lastname: Calvo
authors.forename: Serena
authors.initials: S
authors.lastname: Totaro
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Dagorn
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Dusetti
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004317:Doxorubicin / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D014018:Tissue Distribution; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; C429767:TP53INP1 protein, human; C498965:Trp53inp1 protein, mouse; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D018631:ras Proteins