The short splice form of Casper/c-FLIP is a major cellular inhibitor of TRAIL-induced apoptosis

FEBS Lett. 2002 Jan 2;510(1-2):37-40. doi: 10.1016/s0014-5793(01)03222-7.


TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a member of the tumor necrosis factor family that selectively induces apoptosis of cancer cells. However, some cancer cells or subpopulations within cancer cell lines are resistant to TRAIL-induced apoptosis. We developed a retroviral cDNA library-based functional cloning approach to unambiguously identify putative inhibitory genes of TRAIL-induced apoptosis. This effort identified the short splice form of Casper/c-FLIP, Casper-S/c-FLIPs, as a major cellular protein that confers resistance to TRAIL-induced apoptosis. Furthermore, we found that Casper deficient embryonic fibroblasts (EFs) were highly sensitive while their wild-type counterparts were completely resistant to TRAIL-induced apoptosis. Retroviral-mediated transduction of Casper-S/c-FLIPs into Casper(-/-) EFs restored resistance to TRAIL. These data suggest that Casper-S/c-FLIPs is a major cellular inhibitor of TRAIL-induced apoptosis.

Publication types

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

MeSH terms

  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cycloheximide / pharmacology
  • Cysteine Proteinase Inhibitors / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Ligands
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • RNA Splicing*
  • Serpins / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Viral Proteins*


  • Apoptosis Regulatory Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Glycoproteins
  • Protein Synthesis Inhibitors
  • Serpins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • interleukin-1beta-converting enzyme inhibitor
  • Cycloheximide