Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Engineered hybrid dimers: Tracking the activation pathway of caspase-7 MOLECULAR CELL Denault, J., Bekes, M., Scott, F. L., Sexton, K. M., Bogyo, M., Salvesen, G. S. 2006; 23 (4): 523-533

    Abstract:

    Caspase-7 is an obligate dimer of catalytic domains, with generation of activity requiring limited proteolysis within a region that separates the large and small chains of each domain. Using hybrid dimers we distinguish the relative contribution of each domain to catalysis by the whole molecule. We demonstrate that the zymogen arises from direct dimerization and not domain swapping. In contrast to previous conclusions, we show that only one of the catalytic domains must be proteolyzed to enable activation. The processed domain of this singly cleaved zymogen has the same catalytic activity as a domain of fully active caspase-7. A transient intermediate of singly cleaved dimeric caspase-7 can be found in a cell-free model of apoptosis induction. However, we see no evidence for an analogous intermediate of the related executioner caspase-3. Our study demonstrates the efficiency by which the executioner caspases are activated in vivo.

    View details for DOI 10.1016/j.molcel.2006.06.020

    View details for Web of Science ID 000240155000008

    View details for PubMedID 16916640

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