The CD95 Type I/Type II model

Bryan C. Barnhart, Elizabeth C. Alappat, Marcus E. Peter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

354 Scopus citations

Abstract

CD95 (APO-1/Fas) has become the prototype of a death domain containing receptor and is the best studied member of the death receptors that activate the extrinsic apoptosis pathway. This pathway is initiated by recruitment and activation of caspase-8, an initiator caspase, in the death-inducing signaling complex (DISC) followed by direct cleavage of downstream effector caspases. In contrast, the intrinsic apoptosis pathway starts from within the cell either by direct activation of caspases or through intracellular changes such as DNA damage resulting in the release of a number of pro-apoptotic factors from the intermembrane space of mitochondria. The release of these factors results in the activation of another initiator caspase, caspase-9, and ultimately in the activation of effector caspases in a protein complex called the apoptosome. In recent years, it has become apparent that there is cross talk between the extrinsic and intrinsic pathway. In the death receptor pathway of apoptosis induction, the best characterized connection between the two pathways is the Bcl-2 family member Bid which translocates to mitochondria after cleavage by caspase-8 causing pro-apoptotic changes. Cells that die through CD95 without help from mitochondria are called Type I cells, whereas cells in which CD95-mediated death relies mostly on the intrinsic pathway are called Type II. This review focuses on recent developments in the delineation of the biochemistry and the physiological function of the two CD95 pathways.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalSeminars in Immunology
Volume15
Issue number3
DOIs
StatePublished - Jun 2003

Keywords

  • CD95
  • DISC
  • Type I/Type II model

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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