Octapeptide repeat region and N-terminal half of hydrophobic region of prion protein (PrP) mediate PrP-dependent activation of superoxide dismutase

• Published in: Biochemical and biophysical research communications 2005-01, Vol.326 (3), p.600-606
• Main Authors: Sakudo, Akikazu, Lee, Deug-chan, Nishimura, Takuya, Li, Shuming, Tsuji, Shoutaro, Nakamura, Toyoo, Matsumoto, Yoshitsugu, Saeki, Keiichi, Itohara, Shigeyoshi, Ikuta, Kazuyoshi, Onodera, Takashi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Base Sequence; Mice; Mutation; Neurons - physiology; Prion disease; Prion protein; Protein Structure, Tertiary; PrP-deficient cell line; PrPC Proteins - genetics; PrPC Proteins - metabolism; Sequence Deletion; Superoxide Dismutase - metabolism; Time Factors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.11.092

Cellular prion protein PrP C contains two evolutionarily conserved domains among mammals; viz., the octapeptide repeat region (OR; amino acid residue 51–90) and the hydrophobic region (HR; amino acid residue 112–145). Accumulating evidence indicates that PrP C acts as an inhibitor of apoptosis and regulator of superoxide dismutase (SOD) activity. To further understand how PrP C activates SOD and prevents apoptosis, we provide evidence here that OR and N-terminal half of HR mediate PrP C-dependent SOD activation and anti-apoptotic function. Removal of the OR (amino acid residue 53–94) enhances apoptosis and decreases SOD activity. Deletion of the N-terminal half of HR (amino acids residue 95–132) abolishes its ability to activate SOD and to prevent apoptosis, whereas that of the C-terminal half of HR (amino acids residue 124–146) has little if any effect on the anti-apoptotic activity and SOD activation. These data are consistent with a model in which the anti-apoptotic and anti-oxidative function of PrP C is regulated by not only OR but also the N-terminal half of HR.