Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin

被引：113

作者：

Edlich, F ^{[1
]}

Weiwad, M ^{[1
]}

Erdmann, F ^{[1
]}

Fanghänel, J ^{[1
]}

Jarczowski, F ^{[1
]}

Rahfeld, JU ^{[1
]}

Fischer, G ^{[1
]}

机构：

[1] Max Planck Res Unit Enzymol Prot Folding, Max Planck Gesell, D-06120 Halle An Der Saale, Germany

来源：

EMBO JOURNAL | 2005年 / 24卷 / 14期

关键词：

apoptosis; Bcl-2; CaM; FK506-binding protein; PPIase;

D O I：

10.1038/sj.emboj.7600739

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2688 / 2699

页数：12

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