ABSTRACT
In this chapter, the authors summarize their work on transglutaminase (TGase) in normal and transformed cells and present evidence for the possible involvement of TGase in growth control in these cells. TGase catalyzes a calcium-dependent acyl transfer reaction between peptide-bound glutaminyl moieties and primary amines, producing new γ-amide bonds of glutamic acid and ammonia. Membrane integrity or lack of it can reflect protein conformation via post-translational modification, i.e., polymerization through isopeptide bond formation. Transglutaminase has been implicated in the pathology of both proliferative diseases, e.g., malignancy and nonproliferative diseases, e.g., Alzheimer’s disease or cataracts. One facet of the proposed model is that modulation of the substrate for transglutaminase could control isopeptide bond formation. For example, most primary amines can serve as substrates for the enzyme and some have been shown to be effective inhibitors of isopeptide bond formation. Studies using the transformed cell lines involved the use of inhibitors of polyamine biosynthesis.
