JAC, a direct target of oncogenic transcription factor Jun, is involved incell transformation and tumorigenesis

Citation
M. Hartl et al., JAC, a direct target of oncogenic transcription factor Jun, is involved incell transformation and tumorigenesis, P NAS US, 98(24), 2001, pp. 13601-13606
Citations number
42
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
98
Issue
24
Year of publication
2001
Pages
13601 - 13606
Database
ISI
SICI code
0027-8424(20011120)98:24<13601:JADTOO>2.0.ZU;2-T
Abstract
Using subtractive hybridization techniques, we have isolated a gene termed JAC that is strongly and specifically activated in avian fibroblasts transf ormed by the v-jun oncogene of avian sarcoma virus 17 (ASV17), but not in c ells transformed by other oncogenic agents. Furthermore, JAC is highly expr essed in cell lines derived from jun-induced avian fibrosarcomas. Kinetic a nalysis using a doxycycline-control led conditional cell transformation sys tem showed that expression of the 0.8-kb JAC mRNA is induced rapidly upon a ctivation of the oncogenic v-jun allele. Nucleotide sequence analysis and t ranscriptional mapping revealed that the JAC gene contains two exons, with the longest ORF confined to exon 2. The deduced 68-amino acid chicken JAC p rotein is rich in cysteine residues and displays 37% sequence identity to m ammalian high-sulfur keratin-associated proteins. The promoter region of JA C contains a consensus (5'-TGACTCA-3') and a nonconsensus (5'-TGAGTAA-3') A P-1 binding site in tandem, which are both specifically bound by the Gag-Ju n hybrid protein encoded by ASV17. Mutational analysis revealed that the tw o AP-1 sites confer strong transcriptional activation by Gag-Jun in a syner gistic manner. Ectopic expression of JAC in avian fibroblasts leads to anch orage-independent growth, strongly suggesting that deregulation of JAC is a n essential event in jun-induced cell transformation and tumorigenesis.