Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105

Biochem Biophys Res Commun. 2003 Oct 3;309(4):980-5. doi: 10.1016/j.bbrc.2003.08.104.

Abstract

Casper/c-FLIP is a caspase-8-related molecule critically involved in regulation of death receptor-induced apoptosis. It has been shown that Casper can either promote or antagonize apoptosis and can activate the transcription factor NF-kappaB. The exact functions of Casper are controversial. To further understand how Casper signals, we searched Casper-interacting proteins by yeast two-hybrid screening. This effort identified NF-kappaB1 (p105), an atypical IkappaB molecule and the precursor of NF-kappaB subunit p50. Co-immunoprecipitation experiments indicated that Casper interacted with p105 in 293 cells and this interaction was mediated through the C-terminal IkappaB-like domain (IkappaBgamma). Overexpression of p105 and IkappaBgamma inhibited Casper-induced NF-kappaB activation and potentiated Casper-induced apoptosis. Furthermore, Casper and its C-terminal caspase-like domain inhibited p105 processing into p50. Our findings suggest that p105 is involved in Casper-mediated regulation of apoptosis and NF-kappaB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Line
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Protein Binding
  • Protein Precursors / metabolism*
  • Two-Hybrid System Techniques

Substances

  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Protein Precursors