α-Cleavage of cellular prion protein.
The cellular prion protein (PrP (C) ) is subjected to various processing under physiological and pathological conditions, of which the α-cleavage within the central hydrophobic domain not only disrupts a region critical for both PrP toxicity and PrP (C)  to PrP (Sc)  conversion but also produces the N1 fragment that is neuroprotective and the C1 fragment that enhances the pro-apoptotic effect of staurosporine in one report and inhibits prion in another. The proteases responsible for the α-cleavage of PrP (C)  are controversial. The effect of ADAM10, ADAM17, and ADAM9 on N1 secretion clearly indicates their involvement in the α-cleavage of PrP (C) , but there has been no report of direct PrP (C)  α-cleavage activity with any of the three ADAMs in a purified protein form. We demonstrated that, in muscle cells, ADAM8 is the primary protease for the α-cleavage of PrP (C) , but another unidentified protease(s) must also play a minor role. We also found that PrP (C)  regulates ADAM8 expression, suggesting that a close examination on the relationships between PrP (C)  and its processing enzymes may reveal novel roles and underlying mechanisms for PrP (C)  in non-prion diseases such as asthma and cancer.
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Jingjing
J
Liang
Qingzhong
Q
Kong
D051722:ADAM Proteins / Q000378:metabolism*; D000818:Animals; D006801:Humans; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism; D059748:Proteolysis
D018621:PrPC Proteins; D051722:ADAM Proteins