[CTG-repeat in myotonin protein kinase].
Myotonic dystrophy (DM) is one of the most common inherited neuromuscular diseases in adults with a global incidence of 1 in 20,000 individuals. DM is an autosomal dominant disorder characterized primarily by myotonia and progressive muscle weakness. DM has unique genetic feature of anticipation, that is, increasing disease severity from generation to generation. DM candidate gene encodes a protein kinase (myotonin protein kinase; MtPK) expressed ubiquitously, and nearly all cases of DM displayed expansion (about 100 to 1,000) of the CTG repeat in the 3'-untranslated region, whose repeating number is in proportion to the severity of the condition. The physiological functions, however, of MtPK and the triplet repeat expansion are not yet clear. Thus, to elucidate the molecular mechanism of DM and for therapy of DM at last, we started biochemical analysis of MtPK and molecular biological study of CTG repeat. First of all, we have cloned a full length cDNA for MtPK, which encodes 625 amino acid residues and contains 5 repeats of CTG. Detailed structural analysis of MtPK and expression study of MtPK using the cDNA were performed, and physiological function of MtPK is discussed based on the results.
Sorimachi
H
H
Department of Molecular Biology, University of Tokyo.
Sasagawa
N
N
Maruyama
K
K
Arahata
K
K
Ishiura
S
S
Suzuki
K
K
D000328:Adult; D002478:Cells, Cultured; D005799:Genes, Dominant; D006801:Humans; D018598:Minisatellite Repeats; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis
C585517:DMPK protein, human; D012333:RNA, Messenger; D011494:Protein Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases