NR ARST
AU Sakudo,A.; Lee,D.C.; Nishimura,T.; Li,S.; Tsuji,S.; Nakamura,T.; Matsumoto,Y.; Saeki,K.; Itohara,S.; Ikuta,K.; Onodera,T.
TI Octapeptide repeat region and N-terminal half of hydrophobic region of prion protein (PrP) mediate PrP-dependent activation of superoxide dismutase
QU Biochemical and Biophysical Research Communications 2005 Jan 21; 326(3): 600-6
PT journal article
AB Cellular prion protein PrPc 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 PrPc acts as an inhibitor of apoptosis and regulator of superoxide dismutase (SOD) activity. To further understand how PrPc activates SOD and prevents apoptosis, we provide evidence here that OR and N-terminal half of HR mediate PrPc-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 PrPc is regulated by not only OR but also the N-terminal half of HR.
MH Amino Acid Sequence; Animals; Apoptosis/genetics/physiology; Base Sequence; Mice; Mutation; Neurons/physiology; PrPc Proteins/genetics/*metabolism; Protein Structure, Tertiary; Research Support, Non-U.S. Gov't; Sequence Deletion; Superoxide Dismutase/*metabolism; Time Factors
AD Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
SP englisch
PO USA