title: Polyglutamine domains are substrates of tissue transglutaminase: does transglutaminase play a role in expanded CAG/poly-Q neurodegenerative diseases?
abstract: 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.
authors.affiliation: Department of Biochemistry, Cornell University Medical College, New York, New York, U.S.A.
authors.forename: A J
authors.initials: AJ
authors.lastname: Cooper
authors.forename: K F
authors.initials: KF
authors.lastname: Sheu
authors.forename: J R
authors.initials: JR
authors.lastname: Burke
authors.forename: O
authors.initials: O
authors.lastname: Onodera
authors.forename: W J
authors.initials: WJ
authors.lastname: Strittmatter
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: J P
authors.initials: JP
authors.lastname: Blass
mesh_terms: 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*
chemical_list: D010455:Peptides; C097188:polyglutamine; D011503:Transglutaminases