Abstract
High levels of c-myb expression are necessary for the proliferation of hematopoietic precursor cells whereas down-regulation of c-myb is required for terminal differentiation; this down-regulation occurs through a conditional block to transcriptional elongation in intron I. We previously observed that cAMP analogs prevented the late down-regulation of c-myb during hexamethylene bisacetamide (HMBA)-induced differentiation of murine erythroleukemia (MEL) cells and blocked differentiation; this correlated with the induction of NF-κB (p50/RelB) complexes which were shown to bind to NF-κB recognition sites flanking the transcriptional pause site of c-myb. We now selected stably-transfected MEL cells which overexpressed p50, RelB or both at levels similar to those induced by cAMP to determine whether these NF-κB proteins regulate c-myb expression in intact cells. We demonstrate that transcriptionally active NF-κB (p50/RelB) complexes, but not p50 or RelB alone, prevented the early and late down-regulation of c-myb mRNA and increased c-myb transcriptional elongation in HMBA-induced MEL cells. The increase in c-myb expression was sufficient to block erythroid differentiation and allow continuous proliferation of cells in the presence of HMBA. Steady-state c-myb mRNA levels in untreated cells were not affected by overexpression of NF-κB, suggesting that p50/RelB specifically modulated the efficiency of transcriptional attenuation during MEL cell differentiation.
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Acknowledgements
We are grateful to Drs R Bravo, J DiDonato, M Karin, CD Reddy and EP Reddy for providing us DNA constructs and antibodies. We would like to thank Dr G Boss for helpful discussions. This work was supported by NSF grant MCB-9506327 and NIH grant RO1-GM55586.
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Suhasini, M., Pilz, R. Transcriptional elongation of c-myb is regulated by NF-κB (p50/RelB). Oncogene 18, 7360–7369 (1999). https://doi.org/10.1038/sj.onc.1203158
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DOI: https://doi.org/10.1038/sj.onc.1203158
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