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标题：Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages
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作者：Shomyseh Sanjabi ; Alexander Hoffmann ; Hsiou-Chi Liou 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2000
卷号：97
期号：23
页码：12705-12710
DOI：10.1073/pnas.230436397
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A major challenge in the study of gene regulation by NF-{kappa}B/Rel transcription factors is to understand, at the biological and mechanistic levels, the selective functions of individual Rel family members. To study selectivity, we have examined the NF-{kappa}B/Rel protein binding site (Rel site) within the IL-12 p40 promoter. IL-12 is a proinflammatory cytokine expressed by activated macrophages that serves as an essential inducer of T helper 1 cell development. In nuclear extracts from lipopolysaccharideactivated macrophages, the predominant Rel dimers capable of binding the IL-12 p40 Rel site were the p50/p65 and p50/c-Rel heterodimers and p50/p50 homodimer. The two heterodimers bound the site with comparable affinities and exhibited comparable transactivation activities. In striking contrast, p40 mRNA and protein concentrations were reduced dramatically in c-Rel-/- macrophages and only modestly in p65-/- macrophages. Other proinflammatory cytokine mRNAs and proteins were not significantly reduced in c-Rel-/- macrophages. These results reveal that a c-Rel-containing complex is an essential and selective activator of p40 transcription, which may reflect unique regulatory mechanisms or biological functions of IL-12. Furthermore, because selectivity was not observed in vitro or in transient transactivation experiments, these findings suggest that an understanding of the selectivity mechanism may require an analysis of the endogenous p40 locus.