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

Author

Listed:
  • Takahiro Maeda

    (Cancer Biology and Genetics Program
    Sloan-Kettering Institute)

  • Robin M. Hobbs

    (Cancer Biology and Genetics Program
    Sloan-Kettering Institute)

  • Taha Merghoub

    (Cancer Biology and Genetics Program
    Sloan-Kettering Institute)

  • Ilhem Guernah

    (Cancer Biology and Genetics Program
    Sloan-Kettering Institute)

  • Arthur Zelent

    (Leukemia Research Fund Center at the Institute of Cancer Research, Chester Beatty Laboratories)

  • Carlos Cordon-Cardo

    (Sloan-Kettering Institute)

  • Julie Teruya-Feldstein

    (Sloan-Kettering Institute)

  • Pier Paolo Pandolfi

    (Cancer Biology and Genetics Program
    Sloan-Kettering Institute)

Abstract

Aberrant transcriptional repression through chromatin remodelling and histone deacetylation has been postulated to represent a driving force underlying tumorigenesis because histone 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 Zbtb7 gene) 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.

Suggested Citation

  • Takahiro Maeda & Robin M. Hobbs & Taha Merghoub & Ilhem Guernah & Arthur Zelent & Carlos Cordon-Cardo & Julie Teruya-Feldstein & Pier Paolo Pandolfi, 2005. "Role of the proto-oncogene Pokemon in cellular transformation and ARF repression," Nature, Nature, vol. 433(7023), pages 278-285, January.
    • Handle: RePEc:nat:nature:v:433:y:2005:i:7023:d:10.1038_nature03203
    DOI: 10.1038/nature03203
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