Role of the proto-oncogene Pokemon in cellular transformation and ARF repression Journal Article
| Authors: | Maeda, T.; Hobbs, R. M.; Merghoub, T.; Guernah, I.; Zelent, A.; Cordon-Cardo, C.; Teruya-Feldstein, J.; Pandolfi, P. P. |
| Article Title: | Role of the proto-oncogene Pokemon in cellular transformation and ARF repression |
| Abstract: | Aberrant transcriptional repression through chromatin remodelling and histone deacetylation has been postulated to represent a driving force underlying tumorigenesis because historic deacetylase inhibitors have been found to be effective in cancer treatment. However, the molecular mechanisms by which transcriptional derepression would be linked to tumour suppression are poorly understood. Here we identify the transcriptional repressor Pokemon (encoded by the Zbtb7gene) as a critical factor in oncogenesis. Mouse embryonic fibroblasts lacking Zbtb7 are completely refractory to oncogene-mediated cellular transformation. Conversely, Pokemon overexpression leads to overt oncogenic transformation both in vitro and in vivo in transgenic mice. Pokemon can specifically repress the transcription of the tumour suppressor gene ARF through direct binding. We find that Pokemon is aberrantly overexpressed in human cancers and that its expression levels predict biological behaviour and clinical outcome. Pokemon's critical role in cellular 'transformation makes it an attractive target for therapeutic intervention. |
| Keywords: | controlled study; gene deletion; dna-binding proteins; histone deacetylase inhibitor; nonhuman; neoplasms; animal cell; mouse; animals; mice; gene targeting; gene overexpression; proto oncogene; apoptosis; genes; down-regulation; genetic transcription; in vivo study; transcription, genetic; in vitro study; carcinogenesis; transgenic mouse; animalia; mus musculus; transcription factors; cell transformation, neoplastic; tumor suppressor gene; gene expression regulation, neoplastic; tumors; histone; cell transformation; chromatin; gene repression; substrate specificity; fibroblasts; molecular structure; arf protein; cyclin-dependent kinase inhibitor p16; tumor suppressor protein p14arf; tumor; repressor proteins; cell aging; biological organs; enzymes; transgenic mice; deacetylation; chromatin assembly and disassembly; cells; proto-oncogenes; transcriptional repression; cellular transformation; oncogenesis; proto-oncogene pokemon; pokemon gene; zbtb7 gene |
| Journal Title: | Nature |
| Volume: | 433 |
| Issue: | 7023 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-01-20 |
| Start Page: | 278 |
| End Page: | 285 |
| Language: | English |
| DOI: | 10.1038/nature03203 |
| PUBMED: | 15662416 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 132" - "Export Date: 24 October 2012" - "CODEN: NATUA" - "Source: Scopus" |
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