Induction of Neuronal Differentiation by p73 in a Neuroblastoma Cell Line

The p53-related p73 andp63 genes encode proteins that share considerable structural and functional homology with p53. Despite similarities, their deletion in mice has different outcomes, implying that the three genes may play distinct roles in vivo. Here we show that endogenous p73 levels increase i...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-05, Vol.275 (20), p.15226-15231
Main Authors: De Laurenzi, Vincenzo, Raschellá, Giuseppe, Barcaroli, Daniela, Annicchiarico-Petruzzelli, Margherita, Ranalli, Marco, Catani, Maria Valeria, Tanno, Barbara, Costanzo, Antonio, Levrero, Massimo, Melino, Gerry
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell Cycle
Cell Differentiation - physiology
DNA-Binding Proteins - genetics
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Genes, p53
Genes, Retinoblastoma
Genes, Tumor Suppressor
Humans
Luciferases - genetics
Mice
N-Myc gene
neural cell adhesion molecule
Neural Cell Adhesion Molecules - genetics
Neurons - cytology
Neurons - physiology
Nuclear Proteins - genetics
p53 gene
p73 gene
Proto-Oncogene Proteins c-myc - genetics
Recombinant Proteins - biosynthesis
retinoblastoma protein
retinoids
Transfection
Tretinoin - pharmacology
Tumor Cells, Cultured
Tumor Protein p73
Tumor Suppressor Proteins
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Summary:The p53-related p73 andp63 genes encode proteins that share considerable structural and functional homology with p53. Despite similarities, their deletion in mice has different outcomes, implying that the three genes may play distinct roles in vivo. Here we show that endogenous p73 levels increase in neuroblastoma cells induced to differentiate by retinoic acid and that exogenously expressed p73, but not p53, is sufficient to induce both morphological (neurite outgrowth) and biochemical (expression of neurofilaments and neural cell adhesion molecule (N-CAM); down-regulation of N-MYC and up-regulation of pRB) markers of neuronal differentiation. This activity is shared, to different extents, by all p73 isoforms, whereas the transcriptionally inactive mutants of p73 isoforms are ineffective. Conversely, blockage of endogenous p73 isoforms with a dominant negative p73 results in the abrogation of retinoid-induced N-CAM promoter-driven transcription. Our results indicate that the p73 isoforms activate a pathway that is not shared by p53 and that is required for neuroblastoma cell differentiation in vitro.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.275.20.15226