T lymphocyte activation initiates the degradation of the CD62L encoding mRNA and increases the transcription of the corresponding gene
T lymphocyte activation initiates the degradation of the CD62L encoding mRNA and increases the transcription of the corresponding gene
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DOI：
10.1016/j.imlet.2004.04.009
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发表时间：
2004-06-15
影响因子：
4.4
通讯作者：
Truffa-Bachi, P
中科院分区：
文献类型：
--
作者：
Mascarell, L;Truffa-Bachi, P
在T细胞活化后，CD62L（细胞粘附分子的选择素家族的成员）被组成性内切蛋白酶蛋白水解切割，随后重新表达。为了确定切割是否调节CD62L基因转录，我们在CD62L基因转录和mRNA稳定性水平上分析了T细胞活化的结果。在这里，我们报告，CD62 L脱落与伴随的上调CD62 L基因转录和相应的mRNA的快速降解。CD62L基因上调、mRNA降解或蛋白质脱落不需要新的蛋白质合成。这三个事件对环孢菌素A（CSA）不敏感，因此不依赖于钙调磷酸酶信号通路。在金属蛋白酶抑制剂的存在下活化T细胞，保护CD62L脱落，不阻止CD62L基因上调或mRNA降解。相反，在没有T细胞活化的情况下，通过化学诱导的钙调蛋白从CD62L胞质尾部解离诱导CD62L脱落对CD62L基因转录或mRNA积累水平没有影响。这些数据表明，转录和转录后事件是专门由T细胞活化，而不是由细胞膜上的CD62L密度调节。(C)2004 Elsevier B.V.保留所有权利。
Following T-cell activation, CD62L, a member of the selectin family of cell adhesion molecules, is proteolytically cleaved by a constitutive endoprotease and subsequently re-expressed. To define whether the cleavage regulates CD62L gene transcription, we have analyzed the outcome of T-cell activation on the level of CD62L gene transcription and mRNA stability. Here, we report that CD62L shedding correlates with the concomitant upregulation of CD62L gene transcription and the rapid degradation of the corresponding mRNA. Novel protein synthesis is not required for CD62L gene upregulation, mRNA degradation or protein shedding. The three events are insensitive to cyclosporin A (CSA) and, thus, do not depend on the calcineurin signaling pathway. Activation of T cells in presence of a metallo-protease inhibitor, that protects CD62L shedding, does not prevent CD62L gene upregulation or mRNA degradation. In contrast induction of CD62L shedding by the chemically-induced dissociation of calmodulin from the CD62L cytosolic tail, in absence of T-cell activation, has no consequences on the levels of CD62L gene transcription or mRNA accumulation. These data demonstrate that the transcriptional and post-transcriptional events are exclusively regulated by T-cell activation and not by the CD62L density on cell membrane. (C) 2004 Elsevier B.V. All rights reserved.