alpha-Cleavage of cellular prion protein

作者：Liang Jingjing; Kong Qingzhong^*

来源：Prion, 2012, 6(5): 453-460.

DOI：10.4161/pri.22511

• prion protein
• protein processing
• ADAM8
• ADAM10
• ADAM17
• ADAM9
• plasminogen
• alpha-cleavage
• C1 fragment
• N1 fragment

The cellular prion protein (PrPC) is subjected to various processing under physiological and pathological conditions, of which the alpha-cleavage within the central hydrophobic domain not only disrupts a region critical for both PrP toxicity and PrPC to PrPSc 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 alpha-cleavage of PrPC are controversial. The effect of ADAM10, ADAM17 and ADAM9 on N1 secretion clearly indicates their involvement in the alpha-cleavage of PrPC, but there has been no report of direct PrPC alpha-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 alpha-cleavage of PrPC, but another unidentified protease(s) must also play a minor role. We also found that PrPC regulates ADAM8 expression, suggesting that a close examination on the relationships between PrPC and its processing enzymes may reveal novel roles and underlying mechanisms for PrPC in non-prion diseases such as asthma and cancer.

• 出版日期2012-12