Franzoso G, Carlson L, Brown K, Daucher M B, Bressler P, Siebenlist U
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
EMBO J. 1996 Jul 1;15(13):3403-12.
This study demonstrates that the NF-kappaB subunit p65 can act like an accessory protein for the serum response factor (SRF) in transfection assays. p65 functionally synergizes with SRF to activate the transcription of a reporter construct dependent only on the serum response element (SRE). The synergy of the two factors requires neither a kappaB motif nor direct contact of p65 with DNA. Consistent with these results, a physical complex containing p65 and SRF is observed in vitro. Synergy of the factors is independent of the previously described activation domains present on p65, ruling out indirect effects of p65, but synergy is dependent on the activation domain of SRF. The complexing of p65 and SRF is mediated by a segment of the SRF DNA binding domain, a region of the protein which has also been reported to inhibit its own activation domain. We speculate that p65, upon direct or facilitated interaction with SRF, may relieve the inhibitory activity of this segment, thus enabling the activation domain of SRF to become fully functional. In contrast to p65, the p50 subunit of NF-kappaB does not interact significantly with SRF, either functionally or physically. The data suggest the intriguing possibility that NF-kappaB may participate in the regulation of SRE-dependent promoters, expanding the range of activities of this rapidly activatable transcription factor.
本研究表明，在转染实验中，核因子-κB亚基p65可作为血清反应因子（SRF）的辅助蛋白发挥作用。p65与SRF在功能上协同作用，以激活仅依赖血清反应元件（SRE）的报告基因构建体的转录。这两个因子的协同作用既不需要κB基序，也不需要p65与DNA直接接触。与这些结果一致，在体外观察到了包含p65和SRF的物理复合物。因子的协同作用独立于p65上先前描述的激活结构域，排除了p65的间接作用，但协同作用依赖于SRF的激活结构域。p65与SRF的复合由SRF DNA结合结构域的一段介导，该蛋白质区域也被报道可抑制其自身的激活结构域。我们推测，p65在与SRF直接或促进相互作用后，可能会解除该片段的抑制活性，从而使SRF的激活结构域能够充分发挥功能。与p65不同，核因子-κB的p50亚基在功能或物理上均不与SRF发生显著相互作用。这些数据表明了一种有趣的可能性，即核因子-κB可能参与SRE依赖性启动子的调控，从而扩大了这种快速激活的转录因子的活性范围。
