A novel Apaf-1-independent putative caspase-2 activation complex

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dc.contributor.authorRead, S.
dc.contributor.authorBaliga, B.
dc.contributor.authorEkert, P.
dc.contributor.authorVaux, D.
dc.contributor.authorKumar, S.
dc.date.issued2002
dc.description© The Rockefeller University Press
dc.description.abstractCVaspase activation is a key event in apoptosis execution. In stress-induced apoptosis, the mitochondrial pathway of caspase activation is believed to be of central importance. In this pathway, cytochrome c released from mitochondria facilitates the formation of an Apaf-1 apoptosome that recruits and activates caspase-9. Recent data indicate that in some cells caspase-9 may not be the initiator caspase in stress-mediated apoptosis because caspase-2 is required upstream of mitochondria for the release of cytochrome c and other apoptogenic factors. To determine how caspase-2 is activated, we have studied the formation of a complex that mediates caspase-2 activation. Using gel filtration analysis of cell lysates, we show that caspase-2 is spontaneously recruited to a large protein complex independent of cytochrome c and Apaf-1 and that recruitment of caspase-2 to this complex is sufficient to mediate its activation. Using substrate-binding assays, we also provide the first evidence that caspase-2 activation may occur without processing of the precursor molecule. Our data are consistent with a model where caspase-2 activation occurs by oligomerization, independent of the Apaf-1 apoptosome.
dc.description.statementofresponsibilityStuart H. Read, Belinda C. Baliga, Paul G. Ekert, David L. Vaux and Sharad Kumar
dc.identifier.citationJournal of Cell Biology, 2002; 159(5):739-745
dc.identifier.doi10.1083/jcb.200209004
dc.identifier.issn0021-9525
dc.identifier.issn1540-8140
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttp://hdl.handle.net/2440/9570
dc.language.isoen
dc.publisherRockefeller Univ Press
dc.source.urihttps://doi.org/10.1083/jcb.200209004
dc.subjectapoptosis
dc.subjectcaspase activation
dc.subjectapoptosome
dc.subjectcaspase-9
dc.subjectinitiator caspase
dc.titleA novel Apaf-1-independent putative caspase-2 activation complex
dc.typeJournal article
pubs.publication-statusPublished

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