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c-FLIPR, a new regulator of death receptor-induced apoptosis

Alexander Golks1, Dirk Brenner, Cornelius Fritsch

  • 1Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

The Journal of Biological Chemistry
|February 11, 2005
PubMed

Insights

Researchers discovered a new protein isoform, c-FLIP(R), involved in regulating cell death. This isoform, similar to c-FLIP(S), is expressed in T cells and plays a role in apoptosis signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • c-FLIPs (c-FLICE inhibitory proteins) regulate apoptosis.
  • Previously, only c-FLIP(L) and c-FLIP(S) were known to be expressed at the protein level.

Purpose of the Study:

  • To investigate the endogenous expression of c-FLIP isoforms.
  • To identify and characterize a novel c-FLIP isoform involved in apoptosis.

Main Methods:

  • Analysis of T and B cell lines and primary human T cells.
  • Identification of c-FLIP(R) splice variant.
  • Investigation of c-FLIP(R) recruitment to the CD95 death-inducing signaling complex.

Main Results:

  • Endogenous expression of a third c-FLIP isoform, c-FLIP(R), was detected in T and B cells and primary human T cells.
  • c-FLIP(R) is a death effector domain-only splice variant.
  • c-FLIP(R) is recruited to the CD95 death-inducing signaling complex upon stimulation.
  • c-FLIP(R) shares properties with c-FLIP(S), including short half-life and induction during T cell activation.

Conclusions:

  • The study demonstrates the endogenous expression of c-FLIP(R).
  • c-FLIP(R) and c-FLIP(S) isoforms have similar roles in death receptor-mediated apoptosis.
  • c-FLIP(R) is a significant regulator in T cell apoptosis.

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