CCAAT/enhancer-binding protein β plays a regulatory role in differentiation and apoptosis of neuroblastoma cells

Abstract

The C/EBPβ (CCAAT/enhancer-binding protein β) 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/EBPβ overexpression on the differentiation and survival of mouse Neuro2A cells. We found that C/EBPβ 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/EBPβ transcriptional activity. As it has been suggested in adipocyte differentiation, here we show that C/EBPβ induces the expression of the endogenous C/EBPα gene and that this protein by itself is also able to induce a differentiated phenotype in Neuro2A cells. Neuronal differentiation induced by C/EBPβ 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/EBPβ 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/EBPβ through activation of the p53 protein and the cdk inhibitor p21.