Article
- The EMBO Journal (2003) 22, 246 - 251
- doi:10.1093/emboj/cdg026
Subject Categories:
Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis
Guillermo de la Cueva-Méndez1, Anthony D. Mills1, Lorena Clay-Farrace1, Ramón Díaz-Orejas2 and Ronald A. Laskey1
- MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, Wellcome Trust Cancer Research UK Institute, Tennis Court Road, Cambridge CB2 1QR and Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK
- Centro de Investigaciones Biológicas (C.S.I.C.), Department of Molecular Microbiology, Velázquez 144, E-28006 Madrid, Spain
Correspondence to:
Guillermo de la Cueva-Méndez, E-mail: gd247@hutchison-mrc.cam.ac.uk
Received 6 September 2002; Accepted 19 November 2002; Revised 19 November 2002
Abstract
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.
Keywords:
- gene therapy,
- Kid,
- Kis,
- parD,
- regulated cell killing
