Identification of Components of the Cell Death Pathway.
Abstract
Genetic experiments in C. elegans have shown that a triad of genes consisting of CED3, CED4, and CED9 is necessary for all 131 apoptotic events occurring during the development of the nematode. Homologues of these genes have been identified in mammals as the caspase Family, Apaf 1, and the Bc1 2 family. Targeted gene studies have shown that most caspases involved in apoptosis have a non redundant function. Apaf4 also seems to be involved in most apoptotic event& On the other hand, the mild phenotypes of the knock out mice for Bc1-2 family members, suggest redundancy within this family. We have characterized a novel Bc-2 homologue, Boo,that is only expressed in the ovaries and epididymis. This tissue specific expression suggests that in mammals the central C.elegans triad has been modified. Particularly the Bc1-2 family has been varied to create tissue specific death effector pathways. It will be interesting to explore the pharmacological possibilities that must exist as a result of this tissue specificity. We have also further characterized caspase 14 by in situ hybridizations and show that it is expressed in areas of the brain and thymus with high levels of apoptosis Caspase 14 is only expressed during mouse development which suggests that caspase 14 is involved in apoptosis during development. We have used conditionally transformed striatal cells to study apoptosis in neuronal systems. Using this system we discovered that wild type Huntingtin protects from multiple apoptotic inducers strongly suggesting that it inhibits the activity or the activation of Caspase-9. We are currently exploiting this system for other neuron specific apoptotic events such as p75 NGF signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA372429
Entities
People
- Claudius Vincenz
Organizations
- University of Michigan