Caspase8 (DED)

Full Name:
Caspase-8
Alternative Names:
CAP4, MACH, MCH5, FLICE, ALPS2B, Casp-8, FLJ17672, MGC78473, CASP8
Function:
Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.
Death Domain Subfamily & Boundary Region:
  • DED : 2-80, 100-177 Seq
Species External DB Questionmark
Uniprot DIP STRING KEGG IntAct MINT
Human Seq Q14790external db link DIP-30915Nexternal db link Q14790external db link hsa:841external db link Q14790external db link MINT-91645external db link
Mouse Seq O89110external db link DIP-37435Nexternal db link O89110external db link mmu:12370external db link O89110external db link MINT-91569external db link
Rat Seq Q9JHX4external db link Q9JHX4external db link rno:64044external db link
Dog Seq Q38JA9external db link Q38JA9external db link cfa:488473external db link
Zebra fish Seq Q9I8J3external db link Q9I8J3external db link
Not solved yet
Disease Mutation in disease Reference
Breast cancer D302H 15601643
Breast cancer D302H 15998955
Breast cancer D302H 17293864
Caspase8 deficiency R248W 12353035
Hepatocellualr carcinoma 15531912
Lung, Esophageal, Gastric, Colorectal, Cervical, Breast cancer 17450141
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DED Caspase8 Link Caspase8 Yeast two-hybrid Mouse 1-202 Yeast Mouse 1-202 Yeast 10526240
DED Caspase8 Link Caspase8 Yeast two-hybrid Mouse 1-202 Yeast Mouse 82-202 Yeast 10526240
DED Caspase8 Link DEDD GST fusion protein pull-down Not specified Full length In vitro translation Human 1-318 In vitro translation 9774341
DED Caspase8 Link DEDD GST fusion protein pull-down Not specified 1-180 In vitro translation Human 1-318 In vitro translation 9774341
DED Caspase8 Link DEDD GST fusion protein pull-down Not specified 1-201 In vitro translation Not specified Full length E.coli 11965497
DED Caspase8 Link DEDD2 GST fusion protein pull-down Not specified 1-201 In vitro translation Not specified Full length E.coli 11965497
DED Caspase8 Link FADD Fluorescence resonance energy transfer ` 11717445
DED Caspase8 Link FADD GST fusion protein pull-down HuH-7 lysate Not specified Full length E.coli 12407100
DED Caspase8 Link FADD His fusion protein pull-down Not specified 1-479 In vitro translation Not specified Full length Not specified 8681377
DED Caspase8 Link FADD His fusion protein pull-down Human Not specified In vitro translation Not specified Not specified Not specified 9045686
DED Caspase8 Link FADD His fusion protein pull-down Human 1-479 In vitro translation Not specified Not specified In vitro translation 12010809
DED Caspase8 Link FADD In vitro purification protein assembly(2D gel electrophoresis) Not specified 1-479 In vitro translation Not specified Full length HEK293 8681377
DED Caspase8 Link FADD Yeast two-hybrid Human Not specified Yeast Human Full length Yeast 8681376
DED Caspase8 Link FADD Yeast two-hybrid Human Not specified Yeast Human 1-79 Yeast 8681376
DED Caspase8 Link FADD Yeast two-hybrid Mouse 1-202 Yeast Mouse 1-96 Yeast 10526240
DED Caspase8 Link FADD Yeast two-hybrid Human Full length Yeast Not specified Not specified Yeast 15782135
DED Caspase8 Link FLIP GST fusion protein pull-down Not specified 1-201 In vitro translation Human Full length Not specified 9228018
DED Caspase8 Link FLIP Yeast two-hybrid Human Full length Yeast Human 1-215 Yeast 9208847
DED Caspase8 Link FLIP Yeast two-hybrid Not specified 1-201 Yeast Human 1-160 Yeast 9228018
DED Caspase8 Link FLIP Yeast two-hybrid Not specified Not specified Yeast Human Full length Yeast 9289491
DED Caspase8 Link FLIP Yeast two-hybrid Not specified 1-480 In vitro translation Human 1-208 Not specified 9326610
DED Caspase8 Link FLIP Yeast two-hybrid Not specified 1-216 In vitro translation Human 1-180 Not specified 9326610
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DED Caspase8 Link Caspase10 Co-immunoprecipitation HT1080 12887920
DED Caspase8 Link Caspase10 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 12887920
DED Caspase8 Link Caspase10 Co-immunoprecipitation SKW6.4 17159907
DED Caspase8 Link Caspase10 Fluorescence resonance energy transfer Jurkat Not specified Full length Not specified Full length 11717445
DED Caspase8 Link Caspase8 Fluorescence resonance energy transfer Jurkat Not specified Full length Not specified Full length 11717445
DED Caspase8 Link DEDD Co-immunoprecipitation HEK293 Not used Human 1-318 9774341
DED Caspase8 Link DEDD GST fusion protein pull-down HEK293 Not specified Not specified Not specified Not specified 11741985
DED Caspase8 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 11965497
DED Caspase8 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 12527898
DED Caspase8 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified 1-115 12527898
DED Caspase8 Link FADD HSC3 21525013
DED Caspase8 Link FADD Co-immunoprecipitation HEK293 Human Not specified Human Not specified 8681376
DED Caspase8 Link FADD Co-immunoprecipitation T47D Not specified Not specified Human Not specified 9582077
DED Caspase8 Link FADD Co-immunoprecipitation Jurkat A3 11432804
DED Caspase8 Link FADD Co-immunoprecipitation MCF-7 Human 1-276 Not used 12010809
DED Caspase8 Link FADD Co-immunoprecipitation HEK293 Human 2-177 Human 2-208 12220669
DED Caspase8 Link FADD Co-immunoprecipitation HT1080 12887920
DED Caspase8 Link FADD Co-immunoprecipitation HEK293 Not specified Not specified Human Full length 15701651
DED Caspase8 Link FADD Co-immunoprecipitation SKW6.4 17159907
DED Caspase8 Link FADD Co-immunoprecipitation H2009 18485876
DED Caspase8 Link FADD Co-immunoprecipitation Panc-1 18485876
DED Caspase8 Link FADD Co-immunoprecipitation HT-1080 19060883
DED Caspase8 Link FADD Co-immunoprecipitation HT-29 19524512
DED Caspase8 Link FADD Co-immunoprecipitation H2009 20547836
DED Caspase8 Link FADD Co-immunoprecipitation SH-EP 22890322
DED Caspase8 Link FADD Co-immunoprecipitation LAN-5 22890322
DED Caspase8 Link FADD Fluorescence resonance energy transfer HEK293 Not specified Full length Not specified Not specified 11717445
DED Caspase8 Link FLIP Co-immunoprecipitation HEK293 Not specified Not specified Human Full length 9208847
DED Caspase8 Link FLIP Co-immunoprecipitation HEK293 Not specified Not specified Human Full length 9211860
DED Caspase8 Link FLIP Co-immunoprecipitation HEK293 Not specified 1-201 Human Full length 9228018
DED Caspase8 Link FLIP Co-immunoprecipitation HEK293 Human Not specified Not specified Not specified 9380701
DED Caspase8 Link FLIP Co-immunoprecipitation Raji cell Not used Not specified Not specified 12215447
DED Caspase8 Link FLIP Co-immunoprecipitation HT1080 12887920
DED Caspase8 Link FLIP Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 12887920
DED Caspase8 Link FLIP Co-immunoprecipitation SKW6.4 17159907
DED Caspase8 Link PEA15 Co-immunoprecipitation HeLa Human Not specified Human Full length 10442631
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
DED Caspase8 Link FADD Co-immunoprecipitation F25G, F35V (FADD) 9582077
DED Caspase8 Link FADD Co-immunoprecipitation K33Q and K35Q, F25G (FADD) 12220669
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
DED Caspase8 Link FADD β-galactosidase staining Apoptosis (DISC) 8681376
DED Caspase8 Link FADD DNA fragmentation assay Apoptosis (DISC) 11432804
DED Caspase8 Link FADD Propidium iodide staining Apoptosis (DISC) 12010809
DED Caspase8 Link FADD Hoechst staining Apoptosis (DISC) 12887920
DED Caspase8 Link FADD PARP cleaved assay Apoptosis (DISC) 18485876
DED Caspase8 Link FADD MTT assay Apoptosis (DISC) 22890322
DED Caspase8 Link FADD DAPI staining Apoptosis (DISC) 9045686
DED Caspase8 Link FLIP β-galactosidase staining Apoptosis inhibition 9228018
DED Caspase8 Link FLIP Confocal microscopy Apoptosis inhibition 12215447
DED Caspase8 Link PEA15 PARP cleaved assay Apoptosis inhibition 10442631
(Link: click this icon to show interactions only between the two corresponding DDs)