CCAAT/enhancer-binding protein beta plays a regulatory role in differentiation and apoptosis of neuroblastoma cells.
The C/EBPbeta (CCAAT/enhancer-binding protein beta) is a transcription factor that belongs to basic region-leucine zipper class DNA-binding proteins. There is a significant body of evidence that suggests that this protein plays a central role in adipocytic and eosinophilic differentiation. However, there is no information available regarding the role of this transcription factor in the development of mammalian neuronal tissues. In this study, we have examined the effect of C/EBPbeta overexpression on the differentiation and survival of mouse Neuro2A cells. We found that C/EBPbeta induces neuronal differentiation and that this process is inhibited by transfection with the C/EBP homologous protein 10 (CHOP), strongly suggesting that the extension of neurites is indeed due to the C/EBPbeta transcriptional activity. As it has been suggested in adipocyte differentiation, here we show that C/EBPbeta induces the expression of the endogenous C/EBPalpha gene and that this protein by itself is also able to induce a differentiated phenotype in Neuro2A cells. Neuronal differentiation induced by C/EBPbeta requires activation of the phosphatidylinositol 3-kinase signaling pathway, whereas inhibition of the mitogen-activated protein kinase signaling does not have any effect. In addition, we show that C/EBPbeta is expressed in the brain of neonatal rats, suggesting that this protein could play an important role in neuronal maturation. Finally, cell death was also induced by C/EBPbeta through activation of the p53 protein and the cdk inhibitor p21.
Cortés-Canteli
Marta
M
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas-Universidad Autónoma de Madrid, 28029-Madrid, Spain.
Pignatelli
Miguel
M
Santos
Angel
A
Perez-Castillo
Ana
A
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism* / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004789:Enzyme Activation; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C497250:Ddit3 protein, mouse; C497251:Ddit3 protein, rat; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051742:Transcription Factor CHOP