NF-κB/Rel proteins are required for neuronal differentiation of SH-SY5Y neuroblastoma cells

The expression, cellular localization, and activation of the NF-kappa B/Rel transcription factors are altered during neuronal differentiation, but the significance is unclear. Here we investigate the requirement for NF-kappa B/Rel proteins in neuronal differentiation. SH-SY5Y neuroblastoma cells were induced to differentiate with retinoic acid (RA) or 12-O-tetradecanoylphorbol 13-acetate (TPA), and differentiation was demonstrated by morphological criteria and the enhanced expression of Bcl-2. NF-kappa B was transiently activated after the addition of the differentiation inducers before the morphological signs of differentiation and the enhanced Bcl-2 synthesis. The onset of NF-kappa B activation coincided with a significant reduction in the amount of only one of four NF-kappa B-inhibitory proteins examined (I-kappa B beta). In contrast, NF-kappa B activation and the reduction in I-kappa B beta failed to occur in SH-SY5Y cells transformed with I-kappa B alpha M, a dominant-negative inhibitor of NF-kappa B/Rel proteins. These I-kappa B alpha M-expressing cells failed to differentiate into neuronal cell types when treated with RA or TPA, and the increased Bcl-2 synthesis was blocked. Therefore, NF-kappa B/Rel proteins are require(d) for neuronal differentiation of SH-SY5Y neuroblastoma cells.