Gene interactions and pathways from curated databases and text-mining
Mol Cell 2003, PMID: 12620240

Insights into the regulatory mechanism for caspase-8 activation.

Donepudi, Mrudula; Mac Sweeney, Aengus; Briand, Christophe; Grütter, Markus G

In the death receptor induced apoptotic pathway, caspase-8 autocatalytically cleaves itself at specific cleavage sites. To better understand the regulatory mechanisms behind caspase-8 activation, we compared active wild-type caspase-8 (wtC8) and an uncleavable form of procaspase-8 (uncleavable C8). We demonstrate that wtC8 predominantly exists as a monomer and dimerizes in a concentration and inhibitor binding-dependent fashion. The K(D) for dimeric wtC8 is approximately 50 micro M and decreases when inhibitor bound. Uncleavable C8 is mainly monomeric, but a small amount that dimerizes is as active as wtC8. Inhibitor binding does not favor dimerization but induces active site rearrangements in uncleavable C8. Our findings suggest that dimerization is the crucial factor for caspase-8 activation.

Document information provided by NCBI PubMed

Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • Reactome Reaction: CD14 → TLR4 (reaction)
  • Reactome Reaction: TLR3 → TLR3 (reaction)
  • Reactome Reaction: TRADD → CFLAR (reaction)
  • Reactome Reaction: LY96 → TICAM1 (reaction)
  • Reactome Reaction: FADD → FADD (reaction)
  • Reactome Reaction: LY96 → LY96 (reaction)
  • Reactome Reaction: FADD → TICAM1 (reaction)
  • Reactome Reaction: CASP8 → TRADD (indirect_complex)
  • Reactome Reaction: CASP8 → TICAM1 (reaction)
  • Reactome Reaction: CASP8 → TRAF2 (indirect_complex)
  • Reactome Reaction: FADD → RIPK1 (reaction)
  • Reactome Reaction: CASP8 → TLR4 (reaction)
  • Reactome Reaction: LY96 → RIPK1 (reaction)
  • Reactome Reaction: TICAM2 → TICAM2 (reaction)
  • Reactome Reaction: RIPK1 → CFLAR (reaction)
  • Reactome Reaction: RIPK1 → RIPK1 (reaction)
  • Reactome Reaction: CD14 → TLR3 (reaction)
  • Reactome Reaction: RIPK1 → TLR4 (reaction)
  • Reactome Reaction: LY96 → TLR3 (reaction)
  • Reactome Reaction: FADD → TICAM2 (reaction)
  • Reactome Reaction: CASP8 → TLR3 (reaction)
  • Reactome Reaction: FADD → TLR4 (reaction)
  • Reactome Reaction: CASP8 → CFLAR (reaction)
  • Reactome Reaction: CASP8 → LY96 (reaction)
  • Reactome Reaction: TLR4 → TICAM2 (reaction)
  • Reactome Reaction: FADD → TLR3 (reaction)
  • Reactome Reaction: RIPK1 → TLR3 (reaction)
  • Reactome Reaction: CASP8 → TICAM2 (reaction)
  • Reactome Reaction: CASP8 → CFLAR (direct_complex)
  • Reactome Reaction: TLR3 → TICAM2 (reaction)
  • Reactome Reaction: LY96 → TLR4 (reaction)
  • Reactome Reaction: TRAF2 → CFLAR (reaction)
  • Reactome Reaction: FADD → CASP8 (reaction)
  • Reactome Reaction: TLR3 → TICAM1 (reaction)
  • Reactome Reaction: CD14 → TICAM1 (reaction)
  • Reactome Reaction: TLR4 → TLR4 (reaction)
  • Reactome Reaction: FADD → CASP8 (indirect_complex)
  • Reactome Reaction: TICAM1 → TICAM1 (reaction)
  • Reactome Reaction: CD14 → CASP8 (reaction)
  • Reactome Reaction: CD14 → TICAM2 (reaction)
  • Reactome Reaction: CASP8 → RIPK1 (reaction)
  • Reactome Reaction: FADD → CFLAR (reaction)
  • Reactome Reaction: CD14 → CD14 (reaction)
  • Reactome Reaction: TRAF2 → CFLAR (indirect_complex)
  • Reactome Reaction: FADD → CFLAR (indirect_complex)
  • Reactome Reaction: TLR3 → TLR4 (reaction)
  • Reactome Reaction: RIPK1 → TICAM1 (reaction)
  • Reactome Reaction: CD14 → FADD (reaction)
  • Reactome Reaction: TICAM2 → TICAM1 (reaction)
  • Reactome Reaction: FADD → LY96 (reaction)
  • Reactome Reaction: TLR4 → TICAM1 (reaction)
  • Reactome Reaction: LY96 → TICAM2 (reaction)
  • Reactome Reaction: CD14 → RIPK1 (reaction)
  • Reactome Reaction: RIPK1 → CFLAR (indirect_complex)
  • Reactome Reaction: TRADD → CFLAR (indirect_complex)
  • Reactome Reaction: RIPK1 → TICAM2 (reaction)
  • Reactome Reaction: CD14 → LY96 (reaction)
  • Reactome Reaction: CASP8 → TRAF2 (reaction)
  • Reactome Reaction: CASP8 → RIPK1 (indirect_complex)
  • Reactome Reaction: CASP8 → TRADD (reaction)
  • Reactome Reaction: CASP8 → CASP8 (reaction)
In total, 52 gene pairs are associated to this article in curated databases