Transactivation-deficient DeltaTA-p73 acts as an oncogene.
The recently discovered p53-family member p73 displays significant homology to p53, but data from primary tumors and knockout mice argue against p73 being a classical tumor suppressor. We report on the overexpression of NH(2)-terminally truncated, transactivation-deficient p73 proteins (DeltaTA-p73) in human cancer cells. Moreover, we show that DeltaTA-p73 overexpression results in malignant transformation of NIH3T3 fibroblasts and tumor growth in nude mice, thereby providing the experimental evidence for an oncogenic function of DeltaTA-p73. Apparently, increased expression of NH(2)-terminally truncated p73 isoforms conveys the TP73 gene with oncogenic activity that appears to be actively selected for during tumor development.
Stiewe
Thorsten
T
Centre for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen, Medical School, D-45122 Essen, Germany.
Zimmermann
Sonja
S
Frilling
Andreja
A
Esche
Helmut
H
Pützer
Brigitte M
BM
D016475:3T3 Cells / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D009857:Oncogenes / Q000502:physiology*; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins