When p53 needs p73 to be functional - forced p73 expression induces nuclear accumulation of endogenous p53 protein.
In human neuroblastoma (NB), wild type p53 protein does not elicit its archetypal human tumor suppressive activity so far described. To elucidate this alteration, substantial investigations using NB cell lines have underscored p53 protein nuclear localization defect and/or inappropriate conformation, but no definitive evidence has been provided so far. p73, the first homologue of the p53 gene, locates at the 1p36.3 locus, which is known to be deleted in various human tumors including NB. Unlike p53 mRNA, which specifies a single protein, p73alpha mRNAs encode two types of isoform (TAp73alpha and DeltaNp73alpha) resulting from the use of two different promoters, and eliciting or lacking NH(2)-terminal transactivation domain, respectively. DeltaNp73alpha inhibits p53 pro-apoptotic function in murine developing neurons and is abundantly expressed in human undifferentiated NB tumors. However, critical issues have been raised regarding p73alpha isoform roles, and their possible link to p53 are yet to be clarified in human NB using adenoviral infection approach.
Goldschneider
David
D
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8126, Institut Gustave Roussy, 94805 Villejuif Cedex, France.
Blanc
Etienne
E
Raguenez
Gilda
G
Haddada
Hedi
H
Bénard
Jean
J
Douc-Rasy
Sétha
S
D017209:Apoptosis / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins