Iacobelli M, Wachsman W, McGuire K L
Department of Biology and Molecular Biology Institute, San Diego State University, San Diego, CA 92182, USA.
J Immunol. 2000 Jul 15;165(2):860-8. doi: 10.4049/jimmunol.165.2.860.
IL-2 is the major autocrine and paracrine growth factor produced by T cells upon T cell stimulation. The inducible expression of IL-2 is highly regulated by multiple transcription factors, particularly AP-1, which coordinately activate the promoter. Described here is the ability of the novel basic leucine zipper protein p21SNFT to repress AP-1 activity and IL-2 transcription. A detailed analysis of the repression by p21SNFT repression on the IL-2 promoter distal NF-AT/AP-1 site demonstrates that it can bind DNA with NF-AT and Jun, strongly suggesting that it represses NF-AT/AP-1 activity by competing with Fos proteins for Jun dimerization. The importance of this repression is that p21SNFT inhibits the trans-activation potential of protein complexes that contain Jun, thereby demonstrating an additional level of control for the highly regulated, ubiquitous AP-1 transcription factor and the IL-2 gene.
白细胞介素-2（IL-2）是T细胞受到刺激后产生的主要自分泌和旁分泌生长因子。IL-2的诱导性表达受到多种转录因子的高度调控，尤其是活化蛋白-1（AP-1），它能协同激活启动子。本文描述了新型碱性亮氨酸拉链蛋白p21SNFT抑制AP-1活性和IL-2转录的能力。对p21SNFT对IL-2启动子远端核因子活化T细胞（NF-AT）/AP-1位点的抑制作用进行的详细分析表明，它能与NF-AT和Jun结合DNA，强烈提示它通过与Fos蛋白竞争Jun二聚化来抑制NF-AT/AP-1活性。这种抑制作用的重要性在于，p21SNFT抑制了含有Jun的蛋白复合物的反式激活潜能，从而证明了对高度调控且普遍存在的AP-1转录因子和IL-2基因的额外调控水平。
