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Octapeptide repeat region of prion protein (PrP) is required at an early stage for production of abnormal prion protein in PrP-deficient neuronal cell line
Authors:Sakudo Akikazu  Wu Guoying  Onodera Takashi  Ikuta Kazuyoshi
Affiliation:a Department of Virology, Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan
b Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
Abstract:An abnormal isoform of prion protein (PrPSc), which is composed of the same amino acids as cellular PrP (PrPC) and has proteinase K (PK)-resistance, hypothetically converts PrPC into PrPSc. To investigate the region important for PrPSc production, we examined the levels of PrPSc in PrP gene-deficient cells (HpL3-4) expressing PrPC deleted of various regions including the octapeptide repeat region (OR) or hydrophobic region (HR). After Chandler or Obihiro prion infection, PrPSc was produced in HpL3-4 cells expressing wild-type PrPC or PrPC deleted of HR at an early stage and further reduced to below the detectable level, whereas cells expressing PrPC deleted of OR showed no PrPSc production. The results suggest that OR of PrPC is required for the early step of efficient PrPSc production.
Keywords:Prion protein   PrPSc   PrP gene-deficient cell line
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