Cellular FLICE-Inhibitory Protein Regulates Tissue Homeostasis

Curr Top Microbiol Immunol. 2017;403:119-141. doi: 10.1007/82_2015_448.


Cellular FLICE-inhibitory protein (cFLIP) is structurally related to caspase-8, but lacks its protease activity. Cflip gene encodes several splicing variants including short form (cFLIPs) and long form (cFLIPL). cFLIPL is composed of two death effector domains at the N terminus and a C-terminal caspase-like domain, and cFLIPs lacks the caspase-like domain. Our studies reveal that cFLIP plays a central role in NF-κB-dependent survival signals that control apoptosis and programmed necrosis. Germline deletion of Cflip results in embryonic lethality due to enhanced apoptosis and programmed necrosis; however, the combined deletion of the death-signaling regulators, Fadd and Ripk3, prevents embryonic lethality in Cflip-deficient mice. Moreover, tissue-specific deletion of Cflip reveals cFLIP as a crucial regulator that maintains tissue homeostasis of immune cells, hepatocytes, intestinal epithelial cells, and epidermal cells by preventing apoptosis and programmed necrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Caspase 8 / metabolism*
  • Homeostasis / physiology*
  • Humans
  • NF-kappa B / metabolism
  • Signal Transduction / physiology


  • NF-kappa B
  • Caspase 8