Octapeptide repeat region and N-terminal half of hydrophobic region of prion protein (PrP) mediate PrP-dependent activation of superoxide dismutase.
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.
Sakudo
Akikazu
A
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Lee
Deug-chan
DC
Nishimura
Takuya
T
Li
Shuming
S
Tsuji
Shoutaro
S
Nakamura
Toyoo
T
Matsumoto
Yoshitsugu
Y
Saeki
Keiichi
K
Itohara
Shigeyoshi
S
Ikuta
Kazuyoshi
K
Onodera
Takashi
T
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000502:physiology; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors
D018621:PrPC Proteins; D013482:Superoxide Dismutase