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

• KINO Yoshihiro

  Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo

• KAWAHARA Hiroyuki

  Laboratory of Molecular Structure and Functions, Department of Molecular Biology, Institute of Molec

• MAEDA Tatsuya

  Laboratory of Molecular Structure and Functions, Department of Molecular Biology, Institute of Molec

• Usuki Fusako

  Department Of Clinical Medicine National Institute For Minamata Disease

• Kino Yoshihiro

  Department Of Life Sciences Graduate School Of Arts And Sciences The University Of Tokyo

• Sorimachi Hiroyuki

  Laboratory Of Biological Function Department Of Applied Biological Chemistry Graduate School Of Agri

• Sasagawa Noboru

  Department Of Agricultural Chemistry The University Of Tokyo

• Ishiura Shoichi

  Department Of Life And Cognitive Sciences College Of Arts And Sciences The University Of Tokyo

• Takahashi Nobuhiro

  Department Of Applied Biological Science Tokyo University Of Agriculture And Technology

• Suzuki Koichi

  Laboratory Of Applied Entomology Faculty Of Agriculture Iwate University

• Ishiura Shoichi

  Department of Biochemistry , Graduate School of Pharmaceutical Sciences. Hokkaido University

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