Calcium Blocks Formation of Apoptosome by Preventing Nucleotide Exchange in Apaf-1

Qing Bao, Wenyun Lu, Joshua D. Rabinowitz, Yigong Shi

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)181-192
Number of pages12
JournalMolecular Cell
Volume25
Issue number2
DOIs
StatePublished - Jan 26 2007

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • CELLCYCLE

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