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dc.contributor.authorSlee, EA
dc.contributor.authorHarte, MT
dc.contributor.authorKluck, RM
dc.contributor.authorWolf, BB
dc.contributor.authorCasiano, CA
dc.contributor.authorNewmeyer, DD
dc.contributor.authorWang, HG
dc.contributor.authorReed, JC
dc.contributor.authorNicholson, DW
dc.contributor.authorAlnemri, ES
dc.contributor.authorGreen, DR
dc.contributor.authorMartin, SJ
dc.date.accessioned2020-12-21T03:13:13Z
dc.date.available2020-12-21T03:13:13Z
dc.date.issued1999-01-25
dc.identifier.citationSlee, E. A., Harte, M. T., Kluck, R. M., Wolf, B. B., Casiano, C. A., Newmeyer, D. D., Wang, H. G., Reed, J. C., Nicholson, D. W., Alnemri, E. S., Green, D. R. & Martin, S. J. (1999). Ordering the cytochrome c-initiated caspase cascade: Hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. JOURNAL OF CELL BIOLOGY, 144 (2), pp.281-292. https://doi.org/10.1083/jcb.144.2.281.
dc.identifier.issn0021-9525
dc.identifier.urihttp://hdl.handle.net/11343/257116
dc.description.abstractExit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleOrdering the cytochrome c-initiated caspase cascade: Hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner
dc.typeJournal Article
dc.identifier.doi10.1083/jcb.144.2.281
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleThe Journal of Cell Biology
melbourne.source.volume144
melbourne.source.issue2
melbourne.source.pages281-292
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1240418
melbourne.contributor.authorKluck, Ruth
dc.identifier.eissn1540-8140
melbourne.accessrightsOpen Access


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