Kalkhoven E, Wissink S, van der Saag P T, van der Burg B
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
J Biol Chem. 1996 Mar 15;271(11):6217-24. doi: 10.1074/jbc.271.11.6217.
Interactions between transcription factors are an important means of regulating gene transcription. The present study describes the mutual repression of two transcription factors, the RelA(p65) subunit of NF-kappaB and the progesterone receptor (PR). This trans-repression is shown to occur independent of PR isoform, reporter construct, or cell type used. Together with the demonstration of an interaction between PR and RelA in vitro, these findings suggest that the mutual repression is due to a direct interaction between these proteins. Furthermore, activation of NF-kappaB by tumor necrosis factor-alpha also results in repression of PR, while PR is able to repress tumor necrosis factor-alpha-induced NF-kappaB activity. Since NF-KB-regulating cytokine receptors are expressed in progesterone target tissues, like breast and endometrium, the mutual repression of PR and RelA could play an important role in a wide variety of physiological processes in these tissues, including maintenance of pregnancy, immunosuppression, and tumorigenesis.
转录因子之间的相互作用是调节基因转录的重要方式。本研究描述了两种转录因子——核因子-κB的RelA（p65）亚基和孕激素受体（PR）之间的相互抑制作用。这种反式抑制作用被证明与所使用的PR亚型、报告基因构建体或细胞类型无关。结合PR与RelA在体外相互作用的证明，这些发现表明相互抑制是由于这些蛋白质之间的直接相互作用。此外，肿瘤坏死因子-α激活核因子-κB也会导致PR的抑制，而PR能够抑制肿瘤坏死因子-α诱导的核因子-κB活性。由于调节核因子-κB的细胞因子受体在孕激素靶组织如乳腺和子宫内膜中表达，PR和RelA的相互抑制可能在这些组织的多种生理过程中发挥重要作用，包括维持妊娠、免疫抑制和肿瘤发生。
