Role of the proto-oncogene Pokemon in cellular transformation and ARF repression

Takahiro Maeda, Robin H. Hobbs, Taha Morghoub, Ilhem Guernah, Arthur Zelent, Carlos Cordon-Cardo, Julle Teruya-Feldstein, Pler Paolo Pandolfi

Research output: Contribution to journalArticle

258 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)278-285
Number of pages8
JournalNature
Volume433
Issue number7023
DOIs
StatePublished - Jan 20 2005

ASJC Scopus subject areas

  • General

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    Maeda, T., Hobbs, R. H., Morghoub, T., Guernah, I., Zelent, A., Cordon-Cardo, C., Teruya-Feldstein, J., & Pandolfi, P. P. (2005). Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature, 433(7023), 278-285. https://doi.org/10.1038/nature03203