Identification of Components of the Cell Death Pathway.
Abstract
Programmed cell death has been shown to play a role in breast involution, morphogenesis and cancer. The effector arm of the cell death pathway is a family of cysteine proteases related to interleukin- 1 converting enzyme that has recently been renamed caspases. We have determined for the first time the sequential steps involved in the death pathway engaged by a cell surface receptor (CD-95/Fas/Apo- 1). A pivotal role in this process is played by FLICE, a new receptor associated Caspase. This protease directly associates with the receptor and its substrate specificity is compatible with the hypothesis that it is the protease at the apex of a Caspase cascade. We show that the activation of FLICE can occur autocatalytically due to the remaining proteolytic activity of the zymogen form. FLICE2, a second member of the receptor associated Caspases was also cloned and characterized. Further, viral inihibitors of apoptosis were identified that specifically target the FLICE activation step. While the FLICE Caspases are likely to be also involved in TNFR-l signalling a second death pathway emanating from this receptor was identified that acts through the new adapter molecule RAIDD which recruits Caspase-2 to the receptor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA334085
Entities
People
- Vishva Dixit
Organizations
- University of Michigan