Chimeric caspase molecules with potent cell killing activity in apoptosis-resistant cells.
Cellular defects which prevent apoptotic cell death can result in the generation of hyperproliferative disorders and can prevent the effective treatment of such diseases. The majority of cellular defects which result in apoptosis resistance lie upstream of caspase activation. We have described chimeric caspase molecules consisting of the prodomain of caspase-2 fused to the amino terminus of caspase-3, and which are tagged at the carboxyl terminus with green fluorescent protein (GFP) to allow direct visualisation of transfected cells. Here we show that these chimeric caspase molecules possess potent, rapid cell-killing activity in cell lines which display a range of defects resulting in apoptosis resistance.
Shearwin-Whyatt
L
L
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, South Australia, 5000, Australia.
Baliga
B
B
Doumanis
J
J
Kumar
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis; D019556:COS Cells / Q000187:drug effects / Q000378:metabolism; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D049452:Green Fluorescent Proteins; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D014162:Transfection; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C505407:CASP3 protein, human; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases