| Description: | The Laboratory for Molecular Oncology focuses on genetic engineering of animal cells to improve production of medically relevant bioactive proteins. A large variety of bioactive mammalian proteins are known which have such valuable properties from economic and also medical/therapeutic perspectives that great scientific effort is invested to find ways for controlled production of relatively large quantities. Modern cellular and molecular technologies have enabled identification and isolation of the genes that encode the relevant proteins and such sequences constitute the basic material to genetically engineer cells to manipulate production. In many cases, production of therapeutic proteins requires the use of animal cells because bacteria or even yeast cannot readily produce them in a biologically active form. Frequently, for instance, the initial translational product has to be a precursor protein to allow proper folding of the mature and biologically active end product. The mature protein is excised from such a precursor by endoproteolytic processing. This often occurs at sites of paired basic amino acid residues. Many physiologically important proteins require such processing, e.g. neuropeptides, polypeptide hormones, growth and differentiation factors, growth factor receptors, blood clotting factors, enzymes, viral proteins required to infect cells (e.g. glycoprotein gp160 of the HIV virus, hemagglutinin of influenza virus, etc.). Although predicted some 25 years ago, the responsible endoproteolytic processing enzymes remained elusive. Recently, however, our laboratory discovered the first mammalian proprotein processing enzyme with cleavage specificity for paired basic residues. We called it furin. At present, six furin-like mammalian enzymes are known, each with its own specifications. The discovery of these enzymes may prove to have a major impact in biotechnology, more in particular, in animal cell biotechnology and the controlled production by genetically engineered animal cells of bioactive proteins. |
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