TY - JOUR
T1 - Role of the proto-oncogene Pokemon in cellular transformation and ARF repression
AU - Maeda, Takahiro
AU - Hobbs, Robin H.
AU - Morghoub, Taha
AU - Guernah, Ilhem
AU - Zelent, Arthur
AU - Cordon-Cardo, Carlos
AU - Teruya-Feldstein, Julle
AU - Pandolfi, Pler Paolo
N1 - Funding Information:
Acknowledgements We thank D. Yao, C. Hedvat, M. Dudas, J. Qin and A. Wilton for assistance on TMA preparation, staining and statistical analyses; S. Hasan for assistance with data input and management; K. Manova, C. Farrell and other Molecular Cytology Core Facility members for advice and assistance with IHC; J. Overholser and other Monoclonal Antibody Core Facility staff for help with antibody generation; G. Cattoretti and R. Dalla-Favera for advice; and L. Khandker, L. Dong, M. Hu, L. DiSantis and other P.P.P. laboratory members for assistance and discussion. This work is supported in part by an NCI grant to P.P.P.
PY - 2005/1/20
Y1 - 2005/1/20
N2 - 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.
AB - 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.
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U2 - 10.1038/nature03203
DO - 10.1038/nature03203
M3 - Article
C2 - 15662416
AN - SCOPUS:12744269233
SN - 0028-0836
VL - 433
SP - 278
EP - 285
JO - Nature
JF - Nature
IS - 7023
ER -
