Human epidermal transglutaminase.
Epidermal transglutaminase and its structural consequences were first described by studies of the Massachusetts General Hospital dermatology research laboratories in the early 1970s. The enzyme catalyzes an irreversible and necessary step in epidermal terminal differentiation. These features of the process catalyzed by the enzyme have generated great interest in the control mechanisms for enzyme activity. Like all transglutaminases, the human epidermal enzyme has strict requirements for calcium (or strontium) and for a free sulfhydryl group. It is similar to liver transglutaminase in not requiring proteolytic activation; plasma transglutaminase (factor XIII) requires proteolytic activation. Antibodies produced to human epidermal transglutaminases showed high species specificity and no cross-reaction with the human hair follicle transglutaminase. Purified human epidermal transglutaminase has several-fold increases in its activity after treatment with organic solvents, including dimethylsulfoxide, heating in the presence of calcium, and treatment with chaotropic reagents, such as NaSCN or Nal. The enzyme with enhanced activity has altered gel-filtration characteristics, although it exhibits no major molecular weight changes by SDS-electrophoresis or major immunologic differences with the conventional antibodies for human epidermal transglutaminases. A series of monoclonal antibodies to human epidermal transglutaminase is being prepared to allow detailed analysis of its structural activation and detection of common antigenic sites among transglutaminase that may be masked or not present in conventional antibodies to the enzyme. The ability of solvents, simple chemicals, and drugs to alter the function of transglutaminase allows one to consider safe methods for in vivo modulation of the enzyme and consequent modulation of altered function in human epidermal diseases.
Goldsmith
L A
LA
Dermatology Unit, University of Rochester School of Medicine and Dentistry, Rochester, New York, U.S.A.