Sakudo Akikazu, Lee Deug-chan, Nishimura Takuya, Li Shuming, Tsuji Shoutaro, Nakamura Toyoo, Matsumoto Yoshitsugu, Saeki Keiichi, Itohara Shigeyoshi, Ikuta Kazuyoshi, Onodera Takashi
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Biochem Biophys Res Commun. 2005 Jan 21;326(3):600-6. 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.
细胞朊蛋白PrP(C)在哺乳动物中包含两个进化上保守的结构域；即八肽重复区域（OR；氨基酸残基51 - 90）和疏水区域（HR；氨基酸残基112 - 145）。越来越多的证据表明，PrP(C)作为细胞凋亡的抑制剂和超氧化物歧化酶（SOD）活性的调节剂。为了进一步了解PrP(C)如何激活SOD并防止细胞凋亡，我们在此提供证据表明，OR和HR的N端一半介导了PrP(C)依赖的SOD激活和抗凋亡功能。去除OR（氨基酸残基53 - 94）会增强细胞凋亡并降低SOD活性。删除HR的N端一半（氨基酸残基95 - 132）会消除其激活SOD和防止细胞凋亡的能力，而删除HR的C端一半（氨基酸残基124 - 146）对其抗凋亡活性和SOD激活几乎没有影响。这些数据与一个模型一致，即PrP(C)的抗凋亡和抗氧化功能不仅受OR调控，还受HR的N端一半调控。
