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Polyglutamine Domains Are Substrates of Tissue Transglutaminase: Does Transglutaminase Play a Role in Expanded CAG/Poly‐Q Neurodegenerative Diseases?
Author(s) -
Cooper Arthur J. L.,
Sheu KwanFu Rex,
Burke James R.,
Onodera Osamu,
Strittmatter Warren J.,
Roses Allen D.,
Blass John P.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69010431.x
Subject(s) - tissue transglutaminase , enzyme , glutathione , fusion protein , biochemistry , biology , chemistry , gene , recombinant dna
Huntington's disease and six other neurodegenerative diseases are associated with abnormal gene products containing expanded polyglutamine (poly‐Q; Q n ) domains (n ≥ 40). In the present work, we show that glutathione S ‐transferase (GST) fusion proteins containing a small, physiological‐length poly‐Q domain (GSTQ 10 ) or a large, pathological‐length poly‐Q domain (GSTQ 62 ) are excellent substrates of guinea pig liver (tissue) transglutaminase and that both GSTQ 10 and GSTQ 62 are activators of tissue transglutaminase‐catalyzed hydroxaminolysis of N ‐α‐carbobenzoxyglutaminylglycine. The present findings have implications for understanding the pathophysiological mechanisms of expanded CAG/poly‐Q domain diseases.