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- Title
WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential.
- Authors
Reiter, F.; Hartl, M.; Karagiannidis, A. I.; Bister, K.
- Abstract
We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc–Max complex and a binding site for transcription factor C/EBPα. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPα bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPα-binding site are essential for strong transcriptional activation, and that Myc and C/EBPα synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.Oncogene (2007) 26, 1769–1779. doi:10.1038/sj.onc.1209975; published online 11 September 2006
- Subjects
MESSENGER RNA; FIBROBLASTS; GENE expression; POLYCYSTIC kidney disease; CELL transformation; TRANSCRIPTION factors
- Publication
Oncogene, 2007, Vol 26, Issue 12, p1769
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1209975