TAILIEUCHUNG - Báo cáo khoa học: Novel aggregate formation of a frame-shift mutant protein of tissue-nonspecific alkaline phosphatase is ascribed to three cysteine residues in the C-terminal extension

In the majority of hypophosphatasia patients, reductions in the serum lev-els of alkaline phosphatase activity are caused by various missense muta-tions in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. A unique frame-shift mutation due to a deletion of T at cDNA number 1559 [TNSALP (1559delT)] has been reported only in Japanese patients with high allele frequency. | iFEBS Journal Novel aggregate formation of a frame-shift mutant protein of tissue-nonspecific alkaline phosphatase is ascribed to three cysteine residues in the C-terminal extension Retarded secretion and proteasomal degradation Keiichi Komaru1 2 Yoko Ishida1 Yoshihiro Amaya1 Masae Goseki-Sone3 Hideo Orimo4 and Kimimitsu Oda1 5 1 Division of Biochemistry Niigata University Graduate Schoolof Medicaland DentalSciences Gakkocho-dori Niigata Japan 2 Kitasato Junior College of Health and Hygienic Sciences Yamatomachi Minami-Uonuma-shi Niigata Japan 3 Department of Food and Nutrition Japan Women s University Mejirodai Bunkyo-ku Tokyo Japan 4 Department of Biochemistry and Molecular Biology Nippon Medical School Tokyo Japan 5 Center for Transdisciplinary Research Niigata University Japan Keywords aggregation alkaline phosphatase degradation hypophosphatasia proteasome ubiquitin Correspondence K. Oda Division of Biochemistry Course for OralLife Science Niigata University Graduate Schoolof Medicaland Dental Sciences 2-5274 Gakkocho-dori Niigata 951-8514 Japan Fax 81 25 227 2831 Tel 81 25 227 2827 E-mail oda@ Received 21 December 2004 revised 30 January 2005 accepted 3 February 2005 doi In the majority of hypophosphatasia patients reductions in the serum levels of alkaline phosphatase activity are caused by various missense mutations in the tissue-nonspecific alkaline phosphatase TNSALP gene. A unique frame-shift mutation due to a deletion of T at cDNA number 1559 TNSALP 1559delT has been reported only in Japanese patients with high allele frequency. In this study we examined the molecular phenotype of TNSALP 1559delT using in vitro translation translocation system and COS-1 cells transiently expressing this mutant protein. We showed that the mutant protein not only has a larger molecular size than the wild type enzyme by w 12 kDa reflecting an 80 amino acid-long extension at its C-terminus but that it also lacks a .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine