Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin
Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin
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DOI：
10.1038/sj.emboj.7600739
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发表时间：
2005-07-20
期刊：
影响因子：
11.4
通讯作者：
Fischer, G
中科院分区：
文献类型：
--
作者：
Edlich, F;Weiwad, M;Fischer, G
FKBP型肽基脯氨酰顺/反异构酶（PPIases）是参与控制受损的坐骨神经、皮质胆碱能神经元、多巴胺能神经元和5-HT神经元的功能再生的折叠辅助酶。在这里，我们表明，组成型失活的人FK 506结合蛋白38（FKBP 38）能够直接响应细胞内Ca 2+上升，通过形成一个异二聚体的Ca 2 +/钙调素/FKBP 38复合物。只有复合物的形成产生酶活性的FKBP，通过PPI酶位点介导对Bcl-2显示亲和力。Bcl-2与Ca 2 +/钙调素/FKBP 38活性位点之间的关联调节Bcl-2功能，从而参与促进神经元组织中的凋亡。由这种相互作用介导的FKBP 38促凋亡功能被Ca 2 +/钙调蛋白/FKBP 38复合物的PPI酶活性的有效抑制剂或RNA干扰介导的FKBP 38耗竭消除，促进神经元细胞存活。
FKBP-type peptidyl prolyl cis/trans isomerases (PPIases) are folding helper enzymes involved in the control of functional regrowth of damaged sciatic, cortical cholinergic, dopaminergic and 5-HT neurones. Here, we show that the constitutively inactive human FK506-binding protein 38 (FKBP38) is capable of responding directly to intracellular Ca2+ rise through formation of a heterodimeric Ca2+/calmodulin/FKBP38 complex. Only complex formation creates an enzymatically active FKBP, displaying affinity for Bcl-2 mediated through the PPIase site. Association between Bcl-2 and the active site of Ca2+/calmodulin/ FKBP38 regulates Bcl-2 function and thereby participates in the promotion of apoptosis in neuronal tissues. FKBP38 proapoptotic function mediated by this interaction is abolished by either potent inhibitors of the PPIase activity of the Ca2+/calmodulin/ FKBP38 complex or RNA interference-mediated depletion of FKBP38, promoting neuronal cell survival.