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J Biol Chem, Vol. 274, Issue 43, 30341-30344, October 22, 1999
B/Rel Proteins Are Required for Neuronal Differentiation of
SH-SY5Y Neuroblastoma Cells
From the Institute of Molecular and Cell Biology, The National
University of Singapore, Singapore 117609, Republic of
Singapore
The expression, cellular localization, and
activation of the NF-
B/Rel transcription factors are altered during
neuronal differentiation, but the significance is unclear. Here we
investigate the requirement for NF-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-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-B activation coincided with a significant reduction in the amount
of only one of four NF-B-inhibitory proteins examined (I-B
).
In contrast, NF-B activation and the reduction in I-B failed
to occur in SH-SY5Y cells transformed with I-B
M, a
dominant-negative inhibitor of NF-B/Rel proteins. These
I-BM-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-B/Rel proteins are required for neuronal
differentiation of SH-SY5Y neuroblastoma cells.
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