Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade

Peng Li, Deepak Nijhawan, Imawati Budihardjo, Srinivasa M. Srinivasula, Manzoor Ahmad, Emad S. Alnemri, Xiaodong Wang

Research output: Contribution to journalArticle

5733 Citations (Scopus)

Abstract

We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 activation. Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.

Original languageEnglish (US)
Pages (from-to)479-489
Number of pages11
JournalCell
Volume91
Issue number4
StatePublished - Nov 14 1997

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Caspase 9
Cytochromes c
Peptide Hydrolases
Caspase 3
Chemical activation
Caspases
Purification
Catalytic Domain
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91(4), 479-489.

Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. / Li, Peng; Nijhawan, Deepak; Budihardjo, Imawati; Srinivasula, Srinivasa M.; Ahmad, Manzoor; Alnemri, Emad S.; Wang, Xiaodong.

In: Cell, Vol. 91, No. 4, 14.11.1997, p. 479-489.

Research output: Contribution to journalArticle

Li, P, Nijhawan, D, Budihardjo, I, Srinivasula, SM, Ahmad, M, Alnemri, ES & Wang, X 1997, 'Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade', Cell, vol. 91, no. 4, pp. 479-489.
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997 Nov 14;91(4):479-489.
Li, Peng ; Nijhawan, Deepak ; Budihardjo, Imawati ; Srinivasula, Srinivasa M. ; Ahmad, Manzoor ; Alnemri, Emad S. ; Wang, Xiaodong. / Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. In: Cell. 1997 ; Vol. 91, No. 4. pp. 479-489.
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