JAC, a direct target of oncogenic transcription factor Jun, is involved in cell transformation and tumorigenesis.
Using subtractive hybridization techniques, we have isolated a gene termed JAC that is strongly and specifically activated in avian fibroblasts transformed by the v-jun oncogene of avian sarcoma virus 17 (ASV17), but not in cells transformed by other oncogenic agents. Furthermore, JAC is highly expressed in cell lines derived from jun-induced avian fibrosarcomas. Kinetic analysis using a doxycycline-controlled conditional cell transformation system showed that expression of the 0.8-kb JAC mRNA is induced rapidly upon activation of the oncogenic v-jun allele. Nucleotide sequence analysis and transcriptional mapping revealed that the JAC gene contains two exons, with the longest ORF confined to exon 2. The deduced 68-amino acid chicken JAC protein is rich in cysteine residues and displays 37% sequence identity to mammalian high-sulfur keratin-associated proteins. The promoter region of JAC contains a consensus (5'-TGACTCA-3') and a nonconsensus (5'-TGAGTAA-3') AP-1 binding site in tandem, which are both specifically bound by the Gag-Jun hybrid protein encoded by ASV17. Mutational analysis revealed that the two AP-1 sites confer strong transcriptional activation by Gag-Jun in a synergistic manner. Ectopic expression of JAC in avian fibroblasts leads to anchorage-independent growth, strongly suggesting that deregulation of JAC is an essential event in jun-induced cell transformation and tumorigenesis.
Hartl
M
M
Institute of Biochemistry, University of Innsbruck, Peter-Mayr-Strasse 1a, A-6020 Innsbruck, Austria. markus.hartl@uibk.ac.at
Reiter
F
F
Bader
A G
AG
Castellazzi
M
M
Bister
K
K
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D018076:DNA, Complementary; D005347:Fibroblasts / Q000166:cytology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D011784:Quail; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D030161:Avian Proteins; D018076:DNA, Complementary; C442823:JAC protein, Coturnix coturnix; D009363:Neoplasm Proteins; D016759:Oncogene Protein p65(gag-jun); D011506:Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors