Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms
Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms
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正常人 T 细胞激活过程中 4F2 重链基因表达的调节可由多种不同的分子机制介导
DOI：
10.1128/mcb.8.9.3820-3826.1988
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发表时间：
1988
影响因子：
5.3
通讯作者：
J. Leiden
中科院分区：
文献类型：
--
作者：
T. Lindsten;C. June;C. Thompson;J. Leiden
4F 2分子属于在凝集素或抗原介导的T细胞活化后诱导的一组细胞表面抗原。凝集素介导的刺激后4F 2细胞表面表达的增加已被证明伴随着4F 2重链（4F 2 HC）mRNA稳态水平的平行增加。本报告中描述的研究旨在进一步阐明正常静息人外周血T细胞激活后诱导4F 2 HC基因表达的分子机制。静息T细胞中成熟4F 2 HC mRNA的低水平被证明是4F 2 HC基因的外显子1-内含子1区域内转录延伸受阻的结果，而不是启动子失活的结果。佛波醇肉豆蔻酸酯刺激静息T细胞导致稳态4F 2 HC mRNA水平增加20倍，这是通过去除这种转录延长的阻断而介导的。佛波醇肉豆蔻酸酯乙酸酯诱导的4F 2 HC基因表达的增加不同于先前描述的AP-1介导的佛波醇酯诱导的基因表达，因为它需要新的蛋白质合成。用离子霉素加PMA处理静息T细胞导致4F 2 HC mRNA水平增加60倍。这种诱导是由启动子利用率的增加和转录延伸的阻断的去除介导的。最后，通过增加4F 2 HC mRNA的半衰期，放线菌酮处理静息T细胞诱导4F 2 HC基因表达水平增加约5倍，尽管这种机制的生理意义尚不清楚。这些结果表明，正常外周血T细胞中的4F 2 HC基因表达水平可以通过至少三种不同的分子途径进行调节：（i）启动子利用的变化，（ii）转录延长阻滞的调节，和（iii）mRNA稳定性的改变。
The 4F2 molecule belongs to the set of cell surface antigens which is induced following lectin- or antigen-mediated T-cell activation. The increase in 4F2 cell surface expression following lectin-mediated stimulation has been shown to be accompanied by a parallel increase in the steady-state levels of 4F2 heavy-chain (4F2HC) mRNA. The studies described in this report were designed to further elucidate the molecular mechanisms responsible for induction of 4F2HC gene expression following activation of normal resting human peripheral blood T cells. The low levels of mature 4F2HC mRNA in resting T cells were shown to be the result of a block to transcription elongation within the exon 1-intron 1 region of the 4F2HC gene rather than promoter inactivity. Phorbol myristate acetate stimulation of resting T cells resulted in a 20-fold increase in steady-state 4F2HC mRNA levels which was mediated by removal of this block to transcription elongation. The phorbol myristate acetate-induced increase in 4F2HC gene expression is distinct from previously described AP-1-mediated, phorbol ester-induced gene expression in that it requires new protein synthesis. Treatment of resting T cells with ionomycin plus PMA resulted in a 60-fold increase in 4F2HC mRNA levels. This induction was mediated by both an increase in promoter utilization and removal of the block to transcription elongation. Finally, by increasing the half-life of 4F2HC mRNA, cycloheximide treatment of resting T cells induced an approximately five fold increase in the levels of 4F2HC gene expression, although the physiologic significance of this mechanism remains unclear. These results demonstrate that the level of 4F2HC gene expression in normal peripheral blood T cells can be regulated by at least three distinct molecular pathways: (i) changes in promoter utilization, (ii) modulation of a block to transcription elongation, and (iii) alteration in mRNA stability.
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DOI：
10.1016/s0021-9258(17)39661-8
发表时间：
1985-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Peggy J. Farnham;Robert T. Schimke
通讯作者：
Peggy J. Farnham;Robert T. Schimke
单克隆抗体 (4F2) 识别的抗原的表征：人 T 和 B 淋巴母细胞系上的不同分子形式。
DOI：
--
发表时间：
1982
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hemler,ME;Strominger,JL
通讯作者：
Strominger,JL
影响因子：
2.9
作者：
DUGAICZYK, A;HARON, JA;SCHWARTZ, RJ
通讯作者：
SCHWARTZ, RJ
影响因子：
56.9
作者：
LINIAL, M;GUNDERSON, N;GROUDINE, M
通讯作者：
GROUDINE, M