hDLG/SAP97, a member of the MAGUK protein family, is a novel caspase target during cell-cell detachment in apoptosis
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Uroš Gregorc
Abstract
Cell-cell detachment is one of the hallmarks of apoptosis. To date, several transmembrane and plaque proteins from tight and adherent junctions have been characterised as caspase targets during apoptosis. Human discs large protein (hDLG)/SAP97 is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins, localised at the adherent junctions of epithelial and endothelial cells, that is required for adherens junction assembly and differentiation. Here, hDLG is shown to be a caspase target during UV irradiation and staurosporine (STS)-induced apoptosis in HaCaT and CaCo-2 cells. Immunohistological data show a rapid loss of hDLG localisation at the sites of cell-cell contacts, preceding actual cell-cell detachment. In vitro experiments revealed cleavages at multiple sites located in the N-terminal half of the protein by caspase-3 only. Using Ala scanning mutagenesis, one cleavage site with an unusual recognition sequence for the executioner caspases (QSVD427↓N) was identified. These data suggest that caspase-mediated cleavage of hDLG, and other MAGUKs, and their removal from sites of cell-cell contacts is an early step in the disruption of adherens junctions and dismantling of cell-cell contacts during apoptosis.
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Artikel in diesem Heft
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- Rearrangements in a hydrophobic core region mediate cAMP action in the regulatory subunit of PKA
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- A possible alternative mechanism of kinin generation in vivo by cathepsin L
- hDLG/SAP97, a member of the MAGUK protein family, is a novel caspase target during cell-cell detachment in apoptosis
Artikel in diesem Heft
- Digestive versus regulatory proteases: on calpain action in vivo
- Psc3 cohesin of Schizosaccharomyces pombe: cell cycle analysis and identification of three distinct isoforms
- Rearrangements in a hydrophobic core region mediate cAMP action in the regulatory subunit of PKA
- Characterization of oligomeric species in the fibrillization pathway of the yeast prion Ure2p
- Nucleotide binding and filament assembly of recombinant yeast septin complexes
- Identification and partial characterization of two eukaryotic UDP-galactopyranose mutases
- Inhibition of aldosterone biosynthesis by staurosporine
- Rab6 interacts with the mint3 adaptor protein
- Antidiabetic potential of two novel fatty acid derivatised, N-terminally modified analogues of glucose-dependent insulinotropic polypeptide (GIP): N-AcGIP(LysPAL16) and N-AcGIP(LysPAL37)
- Kinetics of autocatalytic zymogen activation measured by a coupled reaction: pepsinogen autoactivation
- A possible alternative mechanism of kinin generation in vivo by cathepsin L
- hDLG/SAP97, a member of the MAGUK protein family, is a novel caspase target during cell-cell detachment in apoptosis