Expression of active, processed ricin in transgenic tobacco

J Biol Chem. 1994 Sep 9;269(36):22473-6.

Abstract

The cDNA encoding the plant toxin precursor preproricin was introduced into tobacco via Agrobacterium tumefaciens-mediated gene transfer. Transgenic plants were assayed for type II ribosome-inactivating protein expression and activity. Western blot analysis of soluble leaf extracts using anti-ricin a-chain (RTA) antibodies identified 34- and 32-kDa proteins, which were electrophoretically indistinguishable from castor seed RTA. Analysis with anti-ricin b-chain (RTB) antibodies identified both a 34-kDa protein major band, which co-migrated with castor seed RTB, and a 30-kDa protein minor band. Enzyme-linked immunoassay of the transgenic leaf extracts with anti-RTA and anti-RTB indicated microgram per gram production on a fresh weight basis of soluble extractable recombinant ricin. Sugar binding enzyme-linked immunoassay employing an immobilized glycoprotein, asialofetuin, and anti-RTB antibodies confirmed the characteristic type II ribosome-inactivating protein galactose binding lectin activity of the recombinant ricin. The enzymatic activity of recombinant ricin was characterized for cell-free translation inhibition, as well as for overall cytotoxicity. A 50% inhibitory dose of 3 x 10(-11) M was observed for the immunoreactive leaf extract material using a rabbit reticulocyte translation inhibition assay, while a 50% lethal dose of 1 x 10(-12) M was calculated with human T-lymphotropic virus-1 infected leukemic T-cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agrobacterium tumefaciens
  • Animals
  • Base Sequence
  • Cell Line
  • Cell Survival / drug effects
  • DNA Primers
  • DNA, Complementary / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Gene Transfer Techniques*
  • Human T-lymphotropic virus 1 / drug effects
  • Human T-lymphotropic virus 1 / physiology
  • Humans
  • Molecular Sequence Data
  • Nicotiana / metabolism*
  • Plant Lectins
  • Plants, Genetically Modified*
  • Plants, Toxic*
  • Plasmids
  • Polymerase Chain Reaction
  • Protein Biosynthesis / drug effects
  • Protein Precursors / biosynthesis*
  • Protein Precursors / isolation & purification
  • Protein Precursors / toxicity
  • Rabbits
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Reticulocytes / drug effects
  • Ricin / biosynthesis*
  • Ricin / isolation & purification
  • Ricin / toxicity
  • Ricinus communis / genetics
  • Ricinus communis / metabolism

Substances

  • DNA Primers
  • DNA, Complementary
  • Plant Lectins
  • Protein Precursors
  • Recombinant Proteins
  • preproricin
  • Ricin