Caspase Pro-Domains and the Regulation of Apoptosis
Abstract
Apoptosis is a program of cellular suicide which results in the removal of damaged or superfluous cells without causing overall changes in tissue architecture. Apoptotic cellular destruction is carried out by a family of proteases known as the caspases. Under many circumstances, apoptotic caspase activation is preceded by release of cytochrome c from the intermembrane space of the mitochondria to the cytosol. Once released, cytochrome c serves as a co-factor in activation of one of the caspases (caspase 9) by a molecule known as Apaf-1. During this funding period, we have made two key findings with respect to regulation of apoptosis: We have identified a novel Apaf-1/pro-caspase 9 interactor known as AFG3L2. We hypothesize that this protein will modulate activation of caspase 9 by cytochrome c. In addition, we have shown that the oncogenic protein Bcr/abl requires kinase activity to protect cells from apoptotic destruction after mitochondrial cytochrome c release. We have also identified a potential cytochrome c interactor whole binding is regulated by Bcr/abl. Collectively, these results should lead to insights into the mechanism of apoptotic cellular destruction.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA389722
Entities
People
- Sally Kornbluth
Organizations
- Duke University Hospital