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：1992
卷号：89
期号：22
页码：10628-10632
DOI：10.1073/pnas.89.22.10628
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The kappa B enhancer serves as a recognition site for the nuclear transcription factor NF-kappa B and other kappa B-specific proteins which are activated in many cell types in response to a variety of extracellular signals. But a steroid-dependent activation of NF-kappa B or any other kappa B-specific protein has not previously been reported, to our knowledge. In this report we demonstrate that estrogen can activate kappa B-specific protein in its target tissue, uterus. We have done this by analyzing the interaction of nuclear extracts with kappa B enhancers, using DNA mobility shift assays. The activation by estradiol was time dependent, reaching a maximum at approximately 2 hr after steroid treatment, and was not inhibited by prior cycloheximide treatment. The protein-DNA complexes formed in response to estradiol did not contain NF-kappa B and, when compared with other kappa B enhancer motifs, had a higher affinity to the kappa B enhancer corresponding to the PRDII element present in duplicate motifs. These protein-DNA complexes also did not appear to contain estrogen receptor, since antibodies to estrogen receptor were without any effect on either their formation or their mobility. The protein-DNA complexes formed in response to estradiol, however, exhibited a high affinity for the estrogen-responsive element, suggesting the participation of an estrogen-receptor-like molecule in the DNA binding. In contrast, the protein-DNA complexes formed constitutively contained NF-kappa B, had equivalent affinities to various kappa B enhancers, and did not have a high affinity for the estrogen-responsive element. On the basis of these findings, we propose that estrogen-dependent activation of the as-yet-unidentified kappa B-specific protein involves the association of this protein with an estrogen-receptor-related molecule and binding of the resulting complex to PRDII. The high affinity and specificity of this binding to PRDII suggests that this may serve as a composite regulatory element in mediating estrogen-dependent gene expression. The potential significance of such a mechanism for steroid hormone action is discussed.
