Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis
Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis
复制标题
DOI：
10.1038/ncb894
复制
发表时间：
2003-01-01
影响因子：
21.3
通讯作者：
Nakayama, KI
中科院分区：
文献类型：
--
作者：
Shirane, M;Nakayama, KI
膜蛋白Bcl-2和Bcl-x（L）的线粒体定位对于它们的抗凋亡功能是必不可少的。在这里，我们表明，线粒体FK 506结合蛋白38（FKBP 38），不像FKBP 12，结合并抑制钙调磷酸酶的免疫抑制剂FK 506的情况下，这表明FKBP 38是这种磷酸酶的固有抑制剂。在免疫沉淀试验中，FKBP 38与Bcl-2和Bcl-x（L）相关，并与这些蛋白质在线粒体中共定位;此外，FKBP 38突变蛋白的表达诱导Bcl-2和Bcl-x（L）的显著再分布。FKBP 38的过表达阻断细胞凋亡，而显性负突变体或RNA干扰对该蛋白的功能抑制促进细胞凋亡。因此，FKBP 38可能通过将Bcl-2和Bcl-x（L）锚定到线粒体来抑制细胞凋亡。
The mitochondrial localization of the membrane proteins Bcl-2 and Bcl-x(L) is essential for their anti-apoptotic function. Here we show that mitochondrial FK506-binding protein 38 (FKBP38), unlike FKBP12, binds to and inhibits calcineurin in the absence of the immunosuppressant FK506, suggesting that FKBP38 is an inherent inhibitor of this phosphatase. FKBP38 is associated with Bcl-2 and Bcl-x(L) in immunoprecipitation assays and colocalizes with these proteins in mitochondria; in addition, the expression of FKBP38 mutant proteins induces a marked redistribution of Bcl-2 and Bcl-x(L). Overexpression of FKBP38 blocks apoptosis, whereas functional inhibition of this protein by a dominant-negative mutant or by RNA interference promotes apoptosis. Thus, FKBP38 might function to inhibit apoptosis by anchoring Bcl-2 and Bcl-x(L) to mitochondria.