Regulation of caspase activation in apoptosis: implications for transformation and drug resistance |
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Authors: | Elizabeth A Slee Seamus J Martin |
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Institution: | (1) Department of Biology, National University of Ireland, Maynooth, Co, Kildare, Ireland |
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Abstract: | Recent developments in the apoptosis field have uncovered a family of cysteine proteases, the Caspases, that act as signalling
components as well as effectors of the cell death machinery. Caspases are constitutively present as inactive precursors within
most cells and undergo proteolytic processing in response to diverse death-inducing stimuli to initiate the death programme.
Active caspases can process other caspases of the same type as well as process caspases further downstream in the pathway
that ultimately leads to collapse of the cell. This cellular collapse is thought to occur as a consequence of caspase-mediated
cleavage of a diverse array of cellular substrates. Regulation of entry into the death programme is controlled at a number
of levels by members of the Bcl-2 family, as well as by other cell death regulatory proteins. Recent data has shed light upon
the mechanism of action of these regulatory molecules and suggests that the point of caspase activation is a major checkpoint
in the cell death programme. Because many transformed cell populations possess derangements in cell death-regulatory genes,
such as bcl-2, such cells frequently exhibit elevated resistance to cytotoxic chemotherapy. Thus, a deeper understanding of
how apoptosis is normally regulated has therapeutic implications for disease states where the normal controls on the cell
death machinery have been subverted.
This revised version was published online in August 2006 with corrections to the Cover Date. |
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Keywords: | apoptosis caspases cell death proteases proteolysis |
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