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Bcl‐2 regulator FKBP38 is activated by Ca 2+ /calmodulin
Author(s) -
Edlich Frank,
Weiwad Matthias,
Erdmann Frank,
Fanghänel Jörg,
Jarczowski Franziska,
Rahfeld JensUlrich,
Fischer Gunter
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600739
Subject(s) - biology , calmodulin , regulator , microbiology and biotechnology , biochemistry , enzyme , gene
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 Ca 2+ rise through formation of a heterodimeric Ca 2+ /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 Ca 2+ /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 Ca 2+ /calmodulin/FKBP38 complex or RNA interference‐mediated depletion of FKBP38, promoting neuronal cell survival.