Induction of transcription from the human immunodeficiency virus 1 long terminal repeat by the RelA (p65) NF-B subunit has been shown to be dependent upon an interaction with the zinc finger DNA-binding domain of Sp1. It was unknown, however, whether NF-B could also interact with other zinc finger-containing transcription factors. In this study we demonstrate that the early growth response transcription factor Egr-1, whose DNA-binding domain shares a high degree of homology with that of Sp1, can also interact with RelA in vitro and regulate NF-B transcriptional activity in vivo. Similar to the interaction with Sp1, the Rel homology domain of RelA interacts with the zinc finger domain of Egr-1. Surprisingly, and in contrast to Sp1, Egr-1 specifically represses RelA transcriptional activity through its zinc finger domain. Moreover, the interaction between RelA and the Egr-1 zinc fingers is mutually exclusive with DNA binding suggesting a model in which Egr-1 directly sequesters NF-B from its target promoters. Because Egr-1 is induced by many of the same stimuli that activate NF-B, this novel transcriptional regulatory mechanism has many implications for the involvement of both factors in cellular processes such as apoptosis and the response to stress and infection.

Activin-A may stimulate tubal decidualization and trophoblast invasion. A better understanding of the mechanism by which an embryo implants in the tubal epithelium may lead to improved methods for early diagnosis and/or management of ectopic pregnancy.

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In humans, the factors that govern the switch from myometrial quiescence to coordinated contractions at the initiation of labor are not well defined. The onset of parturition is itself associated with increases in a number of proinflammatory factors, many of which are regulated by the nuclear factor kappaB (NF-kappaB) family of transcription factors. The expression and DNA-binding activity of NF-kappaB in the myometrium during gestation and parturition were examined. Levels of c-Rel, p50, and p105 NF-kappaB species were dramatically reduced in pregnant myometrium compared with nonpregnant (NP) controls, whereas expression of the RelA subunit remained uniform. Importantly, during labor, expression of all subunits was observed to be significantly reduced in all myometrial samples studied relative to NP levels. Moreover, for RelA, c-Rel, and p50 subunits, there was a gradient of expression between laboring upper (corpus) and lower uterine segment myometrium. No RelB or p52 subunits could be detected. EMSAs identified changes in NF-kappaB subunit composition in the myometrium during pregnancy and labor, with p50 homodimers predominant in NP tissues being replaced with RelA:p50 heterodimers in pregnant and laboring samples. Significantly, RelA was observed to be phosphorylated at serine-536, implicating the involvement of the phosphatidylinositol-3-kinase/AKT pathway in NF-kappaB function in the myometrium.

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