|Title||Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1.|
|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Bao, Q, Lu, W, Rabinowitz, JD, Shi, Y|
|Date Published||2007 Jan 26|
|Keywords||Adenine Nucleotides, Apoptosis, Apoptosomes, Apoptotic Protease-Activating Factor 1, Calcium, Caspase 9, Enzyme Activation, Homeostasis, Humans, In Vitro Techniques, Models, Biological, Protein Conformation, Recombinant Proteins|
Apaf-1 plays an essential role in apoptosis. In the presence of cytochrome c and dATP, Apaf-1 assembles into an oligomeric apoptosome, which is responsible for the activation of procaspase-9 and the maintenance of the enzymatic activity of the processed caspase-9. Regulation of apoptosome assembly by other cellular factors is poorly understood. Here we report that physiological concentrations of calcium ion negatively affect the assembly of apoptosome by inhibiting nucleotide exchange in the monomeric, autoinhibited Apaf-1 protein. Consequently, calcium blocks the ability of Apaf-1 to activate caspase-9. These observations suggest an important role of calcium homeostasis on the Apaf-1-dependent apoptotic pathway.
|Alternate Journal||Mol. Cell|