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Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin.
- Source :
-
The EMBO journal [EMBO J] 2005 Jul 20; Vol. 24 (14), pp. 2688-99. Date of Electronic Publication: 2005 Jun 30. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Apoptosis physiology
Binding Sites
Calmodulin chemistry
Cell Line, Tumor
Circular Dichroism
Humans
Peptidylprolyl Isomerase metabolism
Tacrolimus Binding Proteins antagonists & inhibitors
Tacrolimus Binding Proteins chemistry
Tacrolimus Binding Proteins metabolism
Calcium physiology
Calmodulin physiology
Proto-Oncogene Proteins c-bcl-2 metabolism
Tacrolimus Binding Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 24
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 15990872
- Full Text :
- https://doi.org/10.1038/sj.emboj.7600739