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 proapoptotic effect of staurosporine in one report and inhibits prion in another. The proteases responsible for the α-cleavage of PrPC 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. © 2012 Landes Bioscience.
CITATION STYLE
Liang, J., & Kong, Q. (2012). α-Cleavage of cellular prion protein. Prion. Landes Bioscience. https://doi.org/10.4161/pri.22511
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