DNp73 a matter of cancer: mechanisms and clinical implications.
The p53 family proteins carry on a wide spectrum of biological functions from differentiation, cell cycle arrest, apoptosis, and chemosensitivity of tumors. NH2-terminally truncated p73 (referred to as DNp73) acts as a potent inhibitor of all these tumor suppressor properties, implying that it has oncogenic functions in human tumorigenesis. This was favored by the observation that high DNp73 expression levels in a variety of cancers are associated with adverse clinico-pathological characteristics and the response failure to chemotherapy. The actual challenge is the deciphering of the molecular mechanisms by which DNp73 promotes malignancy and to unravel the regulatory pathways for controlling TP73 isoform expression. This review is focused on recent findings leaving no doubt that N-terminally truncated p73 proteins are operative during oncogenesis, thus underscoring its significance as a marker for disease severity in patients and as target for cancer therapy.
Buhlmann
Sven
S
Department of Vectorology and Experimental Gene Therapy, Biomedical Research Center, University of Rostock Medical School, Schillingallee 69, 18055 Rostock, Germany.
Pützer
Brigitte M
BM
D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins