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

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

Research output: Contribution to journalArticle

252 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Proto-Oncogenes
Carcinogenesis
Neoplasms
Chromatin Assembly and Disassembly
Tumor Suppressor Genes
Oncogenes
Histones
Transgenic Mice
Fibroblasts
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Maeda, T., Hobbs, R. H., Morghoub, T., Guernah, I., Zelent, A. Z., Cordon-Cardo, C., ... 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

Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. / Maeda, Takahiro; Hobbs, Robin H.; Morghoub, Taha; Guernah, Ilhem; Zelent, Arthur Z; Cordon-Cardo, Carlos; Teruya-Feldstein, Julle; Pandolfi, Pler Paolo.

In: Nature, Vol. 433, No. 7023, 20.01.2005, p. 278-285.

Research output: Contribution to journalArticle

Maeda, T, Hobbs, RH, Morghoub, T, Guernah, I, Zelent, AZ, Cordon-Cardo, C, Teruya-Feldstein, J & Pandolfi, PP 2005, 'Role of the proto-oncogene Pokemon in cellular transformation and ARF repression', Nature, vol. 433, no. 7023, pp. 278-285. https://doi.org/10.1038/nature03203
Maeda T, Hobbs RH, Morghoub T, Guernah I, Zelent AZ, Cordon-Cardo C et al. Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature. 2005 Jan 20;433(7023):278-285. https://doi.org/10.1038/nature03203
Maeda, Takahiro ; Hobbs, Robin H. ; Morghoub, Taha ; Guernah, Ilhem ; Zelent, Arthur Z ; Cordon-Cardo, Carlos ; Teruya-Feldstein, Julle ; Pandolfi, Pler Paolo. / Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. In: Nature. 2005 ; Vol. 433, No. 7023. pp. 278-285.
@article{36356e36fb2243b08571c62c1556317f,
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.",
author = "Takahiro Maeda and Hobbs, {Robin H.} and Taha Morghoub and Ilhem Guernah and Zelent, {Arthur Z} and Carlos Cordon-Cardo and Julle Teruya-Feldstein and Pandolfi, {Pler Paolo}",
year = "2005",
month = "1",
day = "20",
doi = "10.1038/nature03203",
language = "English (US)",
volume = "433",
pages = "278--285",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7023",

}

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 Z

AU - Cordon-Cardo, Carlos

AU - Teruya-Feldstein, Julle

AU - Pandolfi, Pler Paolo

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.

UR - http://www.scopus.com/inward/record.url?scp=12744269233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12744269233&partnerID=8YFLogxK

U2 - 10.1038/nature03203

DO - 10.1038/nature03203

M3 - Article

C2 - 15662416

AN - SCOPUS:12744269233

VL - 433

SP - 278

EP - 285

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7023

ER -