Accelerated neuronal differentiation induced by p53 suppression.
p53, a tumor suppressor gene product, has been implicated in the control of cell growth and malignant transformation in different cell types. Here we studied the role of p53 in normal central nervous system development. We show that p53 is expressed in neuroblasts and is down regulated when migrating neurons reach their destination. The suppression of p53 either by the addition of antisense oligonucleotides to culture medium or by the culture of neurons from p53-/- mice accelerated their differentiation. This effect is accompanied by an early induction of MAP1b and a premature dephosphorylation of tau. p53 suppression also reduced levels of p21. Taken collectively these results suggest that the expression of p53 in neuroblasts might prevent neuronal terminal differentiation.
Ferreira
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Department of Medicine (Division Neurology) Brigham and Women's Hospital, Boston MA 02115, USA.
Kosik
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D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D016158:Genes, p53; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D016376:Oligonucleotides, Antisense; D016159:Tumor Suppressor Protein p53; D018844:Cyclin-Dependent Kinases