Castellanos M C, Muñoz C, Montoya M C, Lara-Pezzi E, López-Cabrera M, de Landázuri M O
Servicio de Inmunología, Universidad Autónoma de Madrid, Spain.
J Immunol. 1997 Dec 1;159(11):5463-73.
The leukocyte Ag CD69, one of the earliest cell surface activation Ags, is up-regulated at the transcriptional level by proinflammatory stimuli involving the NF-kappaB/Rel family of transcription factors. However, promoter fragments lacking a critical kappaB motif respond to other stimuli such as phorbol esters and triggering Abs against TCR/CD3. Since the 5' promoter flanking region of the CD69 gene contains several putative binding sequences for transcription factor activating protein-1 (AP-1), we explored its role in the inducible expression of CD69. Stimuli that induce AP-1, but not NF-kappaB, such as pyrrolidine dithiocarbamate, augmented the cell surface expression of CD69 as well as its mRNA levels, and the promoter activity of the CD69 gene. This up-regulation is accompanied by an increased binding of jun and fos family members to a consensus AP-1 binding site of the proximal (-16) CD69 promoter region, which seems to be functionally responsive to different activation signals and is trans activated by c-jun expression vectors. Furthermore, cotransfection of a dominant negative version of c-jun, but not IkappaB, abolished the inducible transcriptional activity of the CD69 promoter. In conclusion, the inducible expression of the CD69 gene by mitogenic signals is regulated by the transcription factor AP-1.
白细胞抗原CD69是最早出现的细胞表面活化抗原之一，在转录水平上由涉及核因子-κB/Rel转录因子家族的促炎刺激上调。然而，缺乏关键κB基序的启动子片段对其他刺激有反应，如佛波酯和抗TCR/CD3的触发抗体。由于CD69基因的5'侧翼启动子区域包含几个转录因子激活蛋白-1（AP-1）的假定结合序列，我们探讨了其在CD69诱导表达中的作用。诱导AP-1而非核因子-κB的刺激，如吡咯烷二硫代氨基甲酸盐，增强了CD69的细胞表面表达及其mRNA水平，以及CD69基因的启动子活性。这种上调伴随着jun和fos家族成员与近端（-16）CD69启动子区域的共有AP-1结合位点的结合增加，该位点似乎对不同的激活信号有功能反应，并被c-jun表达载体反式激活。此外，共转染显性负性形式的c-jun而非IκB，消除了CD69启动子的诱导转录活性。总之，有丝分裂信号诱导的CD69基因表达受转录因子AP-1调控。
