Accession Number : ADA334085

Title :   Identification of Components of the Cell Death Pathway.

Descriptive Note : Annual rept. 1 Jun 96-31 May 97

Corporate Author : MICHIGAN UNIV ANN ARBOR

Personal Author(s) : Dixit, Vishva

PDF Url : ADA334085

Report Date : JUL 1997

Pagination or Media Count : 23

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.

Descriptors :   *COMPUTER PROGRAMMING, *CELLS(BIOLOGY), *BREAST CANCER, ACTIVATION, MOLECULES, ENZYMES, SURFACES, CLONES, HYPOTHESES, ADAPTERS, DEATH, SENSE ORGANS, PEPTIDE HYDROLASES, MORPHOGENESIS.

Subject Categories : Medicine and Medical Research
      Computer Programming and Software

Distribution Statement : APPROVED FOR PUBLIC RELEASE