Advanced search
1 file | 840.71 KB

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

Author
Organization
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.
Keywords
MAGUK, apoptosis, caspase, cathepsin, cell junctions, LYSOSOMAL CYSTEINE PROTEASES, LARGE TUMOR-SUPPRESSOR, TIGHT JUNCTION, CASPASE ACTIVITY, BETA-CATENIN, GRANZYME-B, CLEAVAGE, DEATH, TARGET, LOCALIZATION

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 840.71 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Ivanova, S, U Gregorc, N Vidergar, R Javier, DS Bredt, Peter Vandenabeele, J Pardo, et al. 2011. “MAGUKs, Scaffolding Proteins at Cell Junctions, Are Substrates of Different Proteases During Apoptosis.” Cell Death & Disease 2.
APA
Ivanova, S., Gregorc, U., Vidergar, N., Javier, R., Bredt, D., Vandenabeele, P., Pardo, J., et al. (2011). MAGUKs, scaffolding proteins at cell junctions, are substrates of different proteases during apoptosis. CELL DEATH & DISEASE, 2.
Vancouver
1.
Ivanova S, Gregorc U, Vidergar N, Javier R, Bredt D, Vandenabeele P, et al. MAGUKs, scaffolding proteins at cell junctions, are substrates of different proteases during apoptosis. CELL DEATH & DISEASE. 2011;2.
MLA
Ivanova, S, U Gregorc, N Vidergar, et al. “MAGUKs, Scaffolding Proteins at Cell Junctions, Are Substrates of Different Proteases During Apoptosis.” CELL DEATH & DISEASE 2 (2011): n. pag. Print.
@article{1176638,
  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.},
  articleno    = {e116},
  author       = {Ivanova, S and Gregorc, U and Vidergar, N and Javier, R and Bredt, DS and Vandenabeele, Peter and Pardo, J and Simon, MM and Turk, V and Banks, L and Turk, B},
  issn         = {2041-4889},
  journal      = {CELL DEATH \& DISEASE},
  keyword      = {MAGUK,apoptosis,caspase,cathepsin,cell junctions,LYSOSOMAL CYSTEINE PROTEASES,LARGE TUMOR-SUPPRESSOR,TIGHT JUNCTION,CASPASE ACTIVITY,BETA-CATENIN,GRANZYME-B,CLEAVAGE,DEATH,TARGET,LOCALIZATION},
  language     = {eng},
  pages        = {11},
  title        = {MAGUKs, scaffolding proteins at cell junctions, are substrates of different proteases during apoptosis},
  url          = {http://dx.doi.org/10.1038/cddis.2010.92},
  volume       = {2},
  year         = {2011},
}

Altmetric
View in Altmetric
Web of Science
Times cited: