A novel Apaf-1-independent putative caspase-2 activation complex
Date
2002
Authors
Read, S.
Baliga, B.
Ekert, P.
Vaux, D.
Kumar, S.
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Type:
Journal article
Citation
Journal of Cell Biology, 2002; 159(5):739-745
Statement of Responsibility
Stuart H. Read, Belinda C. Baliga, Paul G. Ekert, David L. Vaux and Sharad Kumar
Conference Name
Abstract
CVaspase 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.
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© The Rockefeller University Press