Rattner A, Korner M, Rosen H, Baeuerle P A, Citri Y
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Mol Cell Biol. 1991 Feb;11(2):1017-22. doi: 10.1128/mcb.11.2.1017-1022.1991.
Upon activation, T lymphocytes accumulate high levels of the neuropeptide enkephalin which correlate with high levels of proenkephalin mRNA in the cells. Here we investigated the transcriptional basis for these changes. The proenkephalin promoter contains a sequence GGGGACGTCCCC, named B2, which is similar to the kappa B sequence GGGGACTTTCC, the binding site of the transcription factor nuclear factor (NF)-kappa B. Activation of T lymphocytes induces an NF-kappa B-like binding activity to the B2 site, concomitant with activation of the proenkephalin promoter. Mutations at the B2 site abolish this transcriptional activation. The purified homodimer (two p50s) of the DNA-binding subunit of NF-kappa B binds the B2 site of proenkephalin relatively better than does the heterotetramer (two p65s plus two p50s) form of the factor. Thus, it appears that the T-cell-specific activation of the proenkephalin promoter is mediated by NF-kappa B. However, as NF-kappa B is ubiquitous and the transcriptional activation through the B2 site is T cell specific, yet another T-cell-specific factor which synergizes with NF-kappa B should be considered.
激活后，T淋巴细胞会积累高水平的神经肽脑啡肽，这与细胞中前脑啡肽mRNA的高水平相关。在此，我们研究了这些变化的转录基础。前脑啡肽启动子包含一个序列GGGGACGTCCCC，命名为B2，它与κB序列GGGGACTTTCC相似，后者是转录因子核因子（NF）-κB的结合位点。T淋巴细胞的激活诱导了一种与B2位点类似NF-κB的结合活性，同时伴随着前脑啡肽启动子的激活。B2位点的突变消除了这种转录激活。NF-κB的DNA结合亚基的纯化同二聚体（两个p50）比该因子的异四聚体（两个p65加两个p50）形式与前脑啡肽的B2位点结合得相对更好。因此，前脑啡肽启动子的T细胞特异性激活似乎是由NF-κB介导的。然而，由于NF-κB是普遍存在的，且通过B2位点的转录激活是T细胞特异性的，因此应该考虑另一种与NF-κB协同作用的T细胞特异性因子。
