Activation of procaspases by FK506 binding protein-mediated oligomerization.
Oligomerization is an important biological mechanism for regulating signal transduction. Activation of caspases during apoptosis is triggered by adaptor protein-mediated oligomerization of initiator procaspases. To facilitate the study of initiator caspase activation, a system that allows inducible activation of various caspases both in vitro and in vivo is highly desired. Here we describe such a caspase activation system that is based on FK506 binding protein (FKBP)-mediated oligomerization. The NH(2)-terminal prodomains of initiator procaspases that facilitate the interaction between procaspases and their adaptor proteins are replaced by a derivative of FKBP called Fv. The Fv-caspase fusions can then be dimerized by a synthetic divalent Fv ligand, AP20187, which binds strongly to Fv but weakly to the endogenous FKBPs. This FKBP-based system may be widely applicable to the study of the regulation and functions of caspases.
Chang
David W
DW
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Yang
Xiaolu
X
D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D019281:Dimerization; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
C463061:AP20187; D018076:DNA, Complementary; D004792:Enzyme Precursors; D011993:Recombinant Fusion Proteins; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus