Functional characterization of the calcipressin motif that suppresses calcineurin-mediated NFAT-dependent cytokine gene expression in human T cells
Functional characterization of the calcipressin motif that suppresses calcineurin-mediated NFAT-dependent cytokine gene expression in human T cells
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DOI：
10.1016/j.cellsig.2005.11.006
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发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Perez-Riba, Merce
中科院分区：
文献类型：
--
作者：
Aubareda, Anna;Mulero, M. Carmen;Perez-Riba, Merce
抑制钙调神经磷酸酶-NFAT信号通路是免疫抑制治疗的主要挑战之一，以避免目前的抗钙调神经磷酸酶药物环孢菌素A和FK 506的严重副作用。钙加压素家族的成员是钙调神经磷酸酶的内源性抑制剂。我们首次描述了两个独立的图案内的人钙加压素1，ELHA和PxIxxT图案，相互作用与钙调磷酸酶在一个独立的功能方式。然而，这里的主要发现是，含有ELHA的钙调神经磷酸酶抑制剂CALP 1（CIC）基序是负责人T细胞中钙调神经磷酸酶介导的NFAT依赖性细胞因子基因表达的体内抑制。我们相信，CIC基序的鉴定可以作为开发用于移植和自身免疫性疾病的新的免疫抑制药物的起点。(c)2005年爱思唯尔公司All rights reserved.
Inhibition of the calcineurin-NFAT signalling pathway is one of the main challenges for immunosuppression therapy to avoid the severe side effects of the current anticalcineurinic drugs, cyclosporin A and FK506. The members of the calcipressin family are endogenous inhibitors of calcineurin. We describe for the first time that two independent motifs within human calcipressin 1, the ELHA and the PxIxxT motifs, interact with calcineurin in an independent functional manner. However, the main finding here is that the ELHA-containing calcineurin-inhibitor CALP1 (CIC) motif is the responsible for the in vivo inhibition of calcineurin-mediated NFAT-dependent cytokine gene expression in human T cells. We believe that the identification of the CIC motif could be used as a starting point for the development of new immunosuppressive drugs for use in transplantation and autoimmune diseases. (c) 2005 Elsevier Inc. All rights reserved.