FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b.
Induction of apoptosis by the cell surface receptor CD95 (APO-1/Fas) has been shown to involve activation of a family of cysteine proteases (caspases). Recently, a new member of this family has been identified, designated FLICE (caspase-8/MACH/Mch5). FLICE is part of the CD95 death-inducing signaling complex and is therefore the most upstream caspase in the CD95 apoptotic pathway. A total of eight different isoforms of FLICE (caspase-8/a-h) have been described. To determine which isoforms are expressed in different cells we have generated a panel of monoclonal antibodies directed against all functional domains of FLICE. Using these antibodies we could show that only two of the FLICE isoforms (caspase-8/a and caspase-8/b) were predominantly expressed in cells of different origin. Both isoforms were recruited to the CD95 death-inducing signaling complex and were activated upon CD95 stimulation with similar kinetics. Taken together, only two of the eight published caspase-8 isoforms could be detected in significant amounts at the protein level.
Scaffidi
C
C
Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Medema
J P
JP
Krammer
P H
PH
Peter
M E
ME
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D017209:Apoptosis; D020170:Caspase 1; D002460:Cell Line; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D003546:Cysteine Endopeptidases; D020170:Caspase 1