Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis.
Plasmid R1 inhibits growth of bacteria by synthesizing an inhibitor of cell proliferation, Kid, and a neutralizing antidote, Kis, which binds tightly to the toxin. Here we report that this toxin and antidote, which have evolved to function in bacteria, also function efficiently in a wide range of eukaryotes. Kid inhibits cell proliferation in yeast, Xenopus laevis and human cells, whilst Kis protects. Moreover, we show that Kid triggers apoptosis in human cells. These effects can be regulated in vivo by modulating the relative amounts of antidote and toxin using inducible eukaryotic promoters for independent transcriptional control of their genes. These findings allow highly regulatable, selective killing of eukaryotic cells, and could be applied to eliminate cancer cells or specific cell lineages in development.
de la Cueva-Méndez
Guillermo
G
MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK. gd247@hutchison-mrc.cam.ac.uk
Mills
Anthony D
AD
Clay-Farrace
Lorena
L
Díaz-Orejas
Ramón
R
Laskey
Ronald A
RA
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002470:Cell Survival; D003603:Cytotoxins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008845:Microinjections; D009876:Operon; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology; D014158:Transcription, Genetic; D014982:Xenopus laevis / Q000196:embryology
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D004268:DNA-Binding Proteins; C068353:Kid protein, Bacteria; C068354:Kis protein, Bacteria; C489749:ParD protein, Plasmid R1; C078613:parD protein, Bacteria