We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A novel Apaf-1-independent putative caspase-2 activation complex.
- Authors
Read, Stuart H.; Baliga, Belinda C.; Ekert, Paul G.; Vaux, David L.; Kumar, Sharad
- Abstract
Caspase 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.
- Subjects
APOPTOSIS; MITOCHONDRIA; CYTOCHROME c
- Publication
Journal of Cell Biology, 2002, Vol 159, Issue 5, p739
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200209004