MAGUKs, scaffolding proteins at cell junctions, are substrates of different proteases during apoptosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-01

AUTHORS

S Ivanova, U Gregorc, N Vidergar, R Javier, D S Bredt, P Vandenabeele, J Pardo, M M Simon, V Turk, L Banks, B Turk

ABSTRACT

A major feature of apoptotic cell death is gross structural changes, one of which is the loss of cell-cell contacts. The caspases, executioners of apoptosis, were shown to cleave several proteins involved in the formation of cell junctions. The membrane-associated guanylate kinases (MAGUKs), which are typically associated with cell junctions, have a major role in the organization of protein-protein complexes at plasma membranes and are therefore potentially important caspase targets during apoptosis. We report here that MAGUKs are cleaved and/or degraded by executioner caspases, granzyme B and several cysteine cathepsins in vitro. When apoptosis was induced by UV-irradiation and staurosporine in different epithelial cell lines, caspases were found to efficiently cleave MAGUKs in these cell models, as the cleavages could be prevented by a pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)fluoromethylketone. Using a selective lysosomal disrupting agent L-leucyl-L-leucine methyl ester, which induces apoptosis through the lysosomal pathway, it was further shown that MAGUKs are also cleaved by the cathepsins in HaCaT and CaCo-2 cells. Immunohistological data showed rapid loss of MAGUKs at the sites of cell-cell contacts, preceding actual cell detachment, suggesting that cleavage of MAGUKs is an important step in fast and efficient cell detachment. More... »

PAGES

e116

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cddis.2010.92

DOI

http://dx.doi.org/10.1038/cddis.2010.92

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020232558

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21368887


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