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

Takahiro Maeda1, Robin M Hobbs, Taha Merghoub

  • 1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA.

Nature
|January 22, 2005
PubMed

Insights

The transcriptional repressor Pokemon (Zbtb7) drives oncogenesis by repressing the tumor suppressor ARF. Inhibiting Pokemon may offer a novel cancer therapy by restoring tumor suppressor function.

Area of Science:

  • Molecular Biology
  • Oncology
  • Epigenetics

Background:

  • Aberrant transcriptional repression via chromatin remodeling and histone deacetylation is implicated in tumorigenesis.
  • Histone deacetylase inhibitors show efficacy in cancer treatment, but mechanisms linking transcriptional derepression to tumor suppression are unclear.

Purpose of the Study:

  • To identify key factors in oncogenesis and understand the molecular mechanisms of transcriptional repression in cancer.
  • To investigate the role of the transcriptional repressor Pokemon (Zbtb7) in cellular transformation and tumorigenesis.

Main Methods:

  • Investigated the function of Zbtb7 in mouse embryonic fibroblasts.
  • Utilized in vitro and in vivo transgenic mouse models to study Pokemon's oncogenic potential.
  • Analyzed Pokemon's direct binding and repression of the ARF tumor suppressor gene.
  • Examined Pokemon expression levels in human cancers.

Main Results:

  • Zbtb7-deficient mouse embryonic fibroblasts were resistant to oncogene-mediated transformation.
  • Pokemon overexpression induced cellular transformation in vitro and in vivo.
  • Pokemon directly binds and represses the transcription of the tumor suppressor gene ARF.
  • Aberrant Pokemon overexpression in human cancers correlates with poor prognosis.

Conclusions:

  • Pokemon (Zbtb7) is a critical oncogenic factor essential for cellular transformation.
  • Pokemon's repression of ARF contributes to its oncogenic activity.
  • Pokemon overexpression in human cancers suggests its potential as a therapeutic target.

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
Reporter Genes02:11

Reporter Genes

Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.
Commonly used reporter...
Transgenic Plants02:50

Transgenic Plants

Recombinant DNA technology called transgenesis is often used to add a foreign gene or remove a detrimental gene from an organism. Such genetically modified organisms are called transgenic organisms.
The first-ever transgenic plant was a tobacco plant developed in 1983 that showed resistance against the tobacco mosaic virus. Since then, many transgenic plants have been developed and commercialized for improving the agricultural, ornamental, and horticultural value of a crop plant. Transgenic...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...