Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin
| Autor: | Frank Edlich, Franziska Jarczowski, Frank Erdmann, Jens-Ulrich Rahfeld, Jörg Fanghänel, Gunter Fischer, Matthias Weiwad |
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| Rok vydání: | 2005 |
| Předmět: |
Calmodulin
Apoptosis Biology Article General Biochemistry Genetics and Molecular Biology Tacrolimus Binding Proteins Cell Line Tumor Humans Binding site Molecular Biology Peptidylprolyl isomerase chemistry.chemical_classification Binding Sites General Immunology and Microbiology Circular Dichroism General Neuroscience Active site RNA Peptidylprolyl Isomerase Cell biology FKBP Enzyme Proto-Oncogene Proteins c-bcl-2 Biochemistry chemistry biology.protein Calcium Intracellular |
| Zdroj: | The EMBO Journal. 24:2688-2699 |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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