title: Identification of p54(nrb) and the 14-3-3 Protein HS1 as TNF-alpha-inducible genes related to cell cycle control and apoptosis in human arterial endothelial cells.
abstract: TNF-alpha plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-alpha induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-alpha on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-alpha cytotoxicity, presumably by NF-kappaB mediated induction of protective genes. However, the cytoprotective genes involved in NF-kappaB dependent endothelial cell survival have not been sufficiently identified. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-alpha inducible genes in human arterial endothelial cells related to cell survival and cell cycle. The TNF-alpha-induced expression of the RNA binding protein p54(nrb) and the 14-3-3 protein HS1 as shown here for the first time may contribute to the TNF-alpha mediated cell protection of endothelial cells. These genes have been shown to play pivotal roles in cell survival and cell cycle control in different experimental settings. The concerted expression of these genes together with other genes related to cell protection and cell cycle like DnaJ, p21(cip1) and the ubiquitin activating enzyme E1 demonstrates the identification of new genes in the context of TNF-alpha induced gene expression patterns mediating the prosurvival effect of TNF-alpha in endothelial cells.
authors.affiliation: Medizinische Poliklinik, University of Bonn, Wilhelmstr. 35-37, 53111 Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stier
authors.forename: Gudrun
authors.initials: G
authors.lastname: Totzke
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gruewald
authors.forename: Thomas
authors.initials: T
authors.lastname: Neuhaus
authors.forename: Stefan
authors.initials: S
authors.lastname: Fronhoffs
authors.forename: Silke
authors.initials: S
authors.lastname: Schoneborn
authors.forename: Hans
authors.initials: H
authors.lastname: Vetter
authors.forename: Yon
authors.initials: Y
authors.lastname: Ko
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001798:Blood Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D050810:Octamer Transcription Factors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013382:Subtraction Technique; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014470:Umbilical Cord
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D004268:DNA-Binding Proteins; C061909:HCLS1 protein, human; D016328:NF-kappa B; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha