Transcriptional elongation of c-myb is regulated by NF-kappaB (p50/RelB).
Transcriptional elongation of c-myb is regulated by NF-kappaB (p50/RelB).
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c-myb 的转录延伸受 NF-kappaB (p50/RelB) 调节。
DOI：
10.1038/sj.onc.1203158
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Pilz,RB
中科院分区：
文献类型：
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作者：
Suhasini,M;Pilz,RB
高水平的c-myb表达是造血前体细胞增殖所必需的，而下调c-myb是终末分化所必需的;这种下调通过内含子I中转录延伸的条件性阻断而发生。我们先前观察到cAMP类似物在双乙酰胺（HMBA）诱导的小鼠红白血病（MEL）细胞分化过程中阻止了c-myB的晚期下调，并阻断了分化;这与NF-κB（p50/RelB）复合物的诱导相关，该复合物显示与c-myB转录暂停位点侧翼的NF-κB识别位点结合。我们现在选择了稳定转染的MEL细胞，这些细胞过表达p50、RelB或两者的水平与cAMP诱导的水平相似，以确定这些NF-κB蛋白是否调节完整细胞中c-myB的表达。我们证明，转录活性NF-κB（p50/RelB）复合物，而不是单独的p50或RelB，阻止HMBA诱导的MEL细胞中c-myB mRNA的早期和晚期下调，并增加c-myB转录延长。c-myb表达的增加足以阻断红系分化并允许细胞在HMBA存在下持续增殖。未处理细胞中稳态c-myB mRNA水平不受NF-κB过表达的影响，表明p50/RelB特异性调节MEL细胞分化过程中转录衰减的效率。
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.