The FLIP Side of Life
- Author(s)
- Silke, J; Strasser, A;
- Details
- Publication Year 2013-01-15,Volume 6,Issue #258,Page pe2
- Journal Title
- SCIENCE SIGNALING
- Publication Type
- Journal Article
- Abstract
- The anti-apoptotic protein c-FLIP, a catalytically inactive homolog of caspase-8, is an important regulator of death receptor signaling. Death receptors constitute a subgroup of the tumor necrosis factor receptor (TNFR) superfamily, which includes TNFR1, Fas, DR4, and DR5. When activated by their respective ligands, TNF, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL), these receptors cause caspase-8-mediated apoptosis. If caspase-8 activity is blocked, however, then these receptors promote death by necroptosis (programmed necrosis), which requires the kinases receptor-interacting kinase 1 (RIPK1) and RIPK3, as well as mixed-lineage kinase-like protein. Necroptosis has become the subject of intense research because it promotes inflammation, and inhibiting this pathway can limit extensive tissue damage and even lethality in inflammatory syndromes. A study now reports on the role of c-FLIP in vivo from experiments with a range of conditional knockout mice and demonstrates that c-FLIP plays a critical role in inhibiting both apoptotic and necroptotic cell death within the whole mouse.
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Keywords
- CHRONIC INTESTINAL INFLAMMATION; CELL-DEATH; TNF-ALPHA; C-FLIP; APOPTOSIS; ACTIVATION; NECROSIS; COMPLEX; PROTEIN
- Research Division(s)
- Cell Signalling And Cell Death
- PubMed ID
- 23322903
- Publisher's Version
- https://doi.org/10.1126/scisignal.2003845
- Terms of Use/Rights Notice
- © 2013 American Association for the Advancement of Science. All Rights Reserved.
Creation Date: 2013-01-15 12:00:00
Last Modified: 2018-03-26 02:20:04