POLYGLUTAMINE DOMAINS ARE SUBSTRATES OF TISSUE TRANSGLUTAMINASE - DOES TRANSGLUTAMINASE PLAY A ROLE IN EXPANDED CAG POLY-Q NEURODEGENERATIVE DISEASES/

Huntington's disease and six other neurodegenerative diseases are asso ciated with abnormal gene products containing expanded polyglutamine ( poly-Q; Q(n)) domains (n > 40). in the present work, we show that glut athione S-transferase (GST) fusion proteins containing a small, physio logical-length poly-Q domain (GSTQ(10)) or a large, pathological-lengt h poly-Q domain (GSTQ(62)) are excellent substrates of guinea pig live r (tissue) transglutaminase and that both GSTQ(10) and GSTQ(62) are ac tivators of tissue transglutaminase-catalyzed hydroxaminolysis of N-al pha-carbobenzoxyglutaminylglycine. The present findings have implicati ons for understanding the pathophysiological mechanisms of expanded CA G/poly-Q domain diseases.