Identification and characterization of genes upregulated in cells transformed by v-Jun.
The transcription factor Jun (c-Jun) functions as a recipient of extracellular growth signals and converts them into patterns of gene expression. An oncogenic variant of c-Jun was isolated from the acutely transforming retrovirus ASV17. Overexpression of this viral Jun (v-Jun) induces transformation of chicken embryo fibroblasts (CEF) in culture and fibrosarcomas in chickens. v-Jun is a constitutively active form of c-Jun and transforms cells presumably by deregulating the expression of specific target genes. In this report, we describe six genes whose transcripts are upregulated in v-Jun-transformed CEF. Three of these genes show homology to known mammalian genes, to MAP kinase phosphatase 2 (MKP-2), to reversion-induced LIM protein (RIL) and to cytokine-inducible SH2-containing protein (CIS). Northern blot analysis, using CEF infected with various Jun mutants or an estrogen-regulatable Jun chimera, revealed distinct induction patterns of individual targets by v-Jun. The chicken RIL homolog showed an expression pattern tightly correlated with the activity of v-Jun. Its expression is also transformation-dependent, suggesting a role for this gene in v-Jun transformation. The newly identified v-Jun targets can serve as molecular markers in the v-Jun transformation process. Oncogene (2000) 19, 3537 - 3545
Department of Molecular and Experimental Medicine, The Scripps Research Institute, BCC239, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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Fu
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Waha
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Vogt
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002461:Cell Line, Transformed / Q000378:metabolism; D002472:Cell Transformation, Viral / Q000235:genetics*; D002642:Chick Embryo; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D054637:Dual-Specificity Phosphatases; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D015723:Gene Library; D016758:Genes, jun; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D060588:LIM Domain Proteins; D051379:Mice; D008840:Microfilament Proteins; D054639:Mitogen-Activated Protein Kinase Phosphatases; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016759:Oncogene Protein p65(gag-jun) / Q000502:physiology*; D016133:Polymerase Chain Reaction; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012190:Retroviridae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013382:Subtraction Technique; D050826:Suppressor of Cytokine Signaling Proteins; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D054637:Dual-Specificity Phosphatases; D017874:Immediate-Early Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D054639:Mitogen-Activated Protein Kinase Phosphatases; D009363:Neoplasm Proteins; D016759:Oncogene Protein p65(gag-jun); D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D011993:Recombinant Fusion Proteins; D050826:Suppressor of Cytokine Signaling Proteins; C486247:PDLIM4 protein, human; C486248:Pdlim4 protein, mouse; C490583:DUSP4 protein, human