Format

Send to

Choose Destination
See comment in PubMed Commons below
Prion. 2012 Nov-Dec;6(5):453-60. doi: 10.4161/pri.22511. Epub 2012 Oct 10.

α-Cleavage of cellular prion protein.

Author information

1
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

Abstract

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.

PMID:
23052041
PMCID:
PMC3510859
DOI:
10.4161/pri.22511
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis Icon for PubMed Central
    Loading ...
    Support Center