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Two hybrid proteins between Pseudomonas aeruginosa exotoxin A (PE) and poliovirus protease 2A pro have been generated. One hybrid protein contains the poliovirus 2A pro sequence replacing the region of PE corresponding to amino acids 413-607. The other hybrid contains in addition the transforming growth factor sequence. The two hybrid proteins were efficiently synthesized in E. coli cells using the inducible pET vectors. Both hybrid toxins cleaved p220 (eIF-4γ) when the recombinant plasmids were transfected in COS cells infected with recombinant vaccinia virus bearing the T7 RNA polymerase gene.