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Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin
Frank Edlich1, Matthias Weiwad, Frank Erdmann
1Max-Planck Research Unit for Enzymology of Protein Folding, Halle/Saale, Germany.
The EMBO Journal
|July 2, 2005
Summary
Calcium influx activates FKBP38, a peptidyl prolyl cis/trans isomerase (PPIase), promoting neuronal apoptosis. Inhibiting FKBP38
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- FKBP-type peptidyl prolyl cis/trans isomerases (PPIases) are crucial for neuronal regrowth.
- FKBP38 is a constitutively inactive enzyme involved in cellular processes.
Purpose of the Study:
- To investigate the mechanism by which FKBP38 becomes active and interacts with Bcl-2.
- To elucidate the role of FKBP38 in neuronal apoptosis.
Main Methods:
- Formation of a Ca2+/calmodulin/FKBP38 complex.
- Assessing FKBP38's affinity for Bcl-2 via its PPIase site.
- Utilizing PPIase inhibitors and RNA interference.
Main Results:
- Intracellular Ca2+ rise activates FKBP38 through Ca2+/calmodulin complex formation.
- Active FKBP38 binds to Bcl-2 at the PPIase site, regulating its function.
- This interaction promotes apoptosis in neuronal tissues.
Conclusions:
- Ca2+/calmodulin-activated FKBP38 plays a proapoptotic role in neurons.
- Inhibition of FKBP38's PPIase activity or its depletion promotes neuronal survival.
- FKBP38 is a potential therapeutic target for neuronal injury.