Coexpression of the CUG-Binding Protein Reduces DM Protein Kinase Expression in COS Cells.
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概要
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Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy. Patients have a large CTG repeat expansion in the 3' untranslated region of the DMPK gene, which encodes DM protein kinase. RNA trans-dominant models, which hypothe-size that the expanded CUG trinucleotide repeat on DMPK mRNA sequesters a factor or disrupts the RNA metabolism of the DMPK mRNA itself and other mRNAs in a trans dominant manner, have been proposed. A candidate for the sequestered factor, termed CUG-binding protein (CUG-BP), exists in several alternatively spliced isoforms. We found a human isoform with a twelve base insertion (deduced amino acids Leu-Tyr-Leu-Gln) and an isoform with a three base insertion (deduced amino acid Ala) insertion. In order to elucidate the effects of CUG-BP on DMPK expression, we introduced CUG-BP and DMPK cDNA transiently into COS-7 cells. Cotransfection of CUG-BP did not signifi-cantly affect the expression of either wild type or mutant DMPK at the mRNA level. On the other hand, cotransfection of CUG-BP significantly affected the expression of both the wild type and mutant DMPKs at the protein level. This reduction was remarkable when the mutant DMPK construct was used.
- 社団法人 日本生化学会の論文
著者
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KINO Yoshihiro
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo
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KAWAHARA Hiroyuki
Laboratory of Molecular Structure and Functions, Department of Molecular Biology, Institute of Molec
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MAEDA Tatsuya
Laboratory of Molecular Structure and Functions, Department of Molecular Biology, Institute of Molec
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Usuki Fusako
Department Of Clinical Medicine National Institute For Minamata Disease
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Kino Yoshihiro
Department Of Life Sciences Graduate School Of Arts And Sciences The University Of Tokyo
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Sorimachi Hiroyuki
Laboratory Of Biological Function Department Of Applied Biological Chemistry Graduate School Of Agri
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Sasagawa Noboru
Department Of Agricultural Chemistry The University Of Tokyo
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Ishiura Shoichi
Department Of Life And Cognitive Sciences College Of Arts And Sciences The University Of Tokyo
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Takahashi Nobuhiro
Department Of Applied Biological Science Tokyo University Of Agriculture And Technology
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Suzuki Koichi
Laboratory Of Applied Entomology Faculty Of Agriculture Iwate University
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Ishiura Shoichi
Department of Biochemistry , Graduate School of Pharmaceutical Sciences. Hokkaido University
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- Coexpression of the CUG-Binding Protein Reduces DM Protein Kinase Expression in COS Cells
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