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 associated with abnormal gene products containing expanded polyglutamine (poly-Q; Qn) domains (n > or = 40). In the present work, we show that glutathione S-transferase (GST) fusion proteins containing a small, physiological-length poly-Q domain (GSTQ10) or a large, pathological-length poly-Q domain (GSTQ62) are excellent substrates of guinea pig liver (tissue) transglutaminase and that both GSTQ10 and GSTQ62 are activators of tissue transglutaminase-catalyzed hydroxaminolysis of N-alpha-carbobenzoxyglutaminylglycine. The present findings have implications for understanding the pathophysiological mechanisms of expanded CAG/poly-Q domain diseases.
Cooper
A J
AJ
Department of Biochemistry, Cornell University Medical College, New York, New York, U.S.A.
Sheu
K F
KF
Burke
J R
JR
Onodera
O
O
Strittmatter
W J
WJ
Roses
A D
AD
Blass
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology; D006168:Guinea Pigs; D008099:Liver / Q000201:enzymology; D009410:Nerve Degeneration / Q000502:physiology*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid; D013379:Substrate Specificity; D011503:Transglutaminases / Q000378:metabolism*
D010455:Peptides; C097188:polyglutamine; D011503:Transglutaminases