Aubareda Anna, Mulero M Carmen, Pérez-Riba Mercè
Medical and Molecular Genetics Center, IDIBELL, Institut de Recerca Oncològica, Gran Via s/n Km 2.7, 08907 Hospitalet de Llobregat, Barcelona, Spain.
Cell Signal. 2006 Sep;18(9):1430-8. doi: 10.1016/j.cellsig.2005.11.006. Epub 2006 Jan 6.
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.
抑制钙调神经磷酸酶-NFAT信号通路是免疫抑制治疗面临的主要挑战之一，目的是避免目前抗钙调神经磷酸酶药物环孢素A和FK506的严重副作用。钙调磷酸酶抑制蛋白家族成员是钙调神经磷酸酶的内源性抑制剂。我们首次描述了人钙调磷酸酶抑制蛋白1内的两个独立基序，即ELHA和PxIxxT基序，以独立的功能方式与钙调神经磷酸酶相互作用。然而，此处的主要发现是，含ELHA的钙调神经磷酸酶抑制剂CALP1（CIC）基序负责在体内抑制人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。我们认为，CIC基序的鉴定可作为开发用于移植和自身免疫性疾病的新型免疫抑制药物的起点。
