Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases

• Published in: Experimental dermatology Vol. 13; no. 11; pp. 700 - 707
• Main Author: Aho, Sirpa
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Munksgaard International Publishers 01.11.2004; Blackwell
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Apoptosis; Biological and medical sciences; caspases; Caspases - metabolism; Cell Adhesion; Cell Nucleus - metabolism; Cytoskeletal Proteins - biosynthesis; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - metabolism; Cytoskeleton - metabolism; Dermatology; desmoplakin; Desmoplakins; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors - pharmacology; Epithelial Cells - metabolism; Humans; Immunoblotting; Intermediate Filament Proteins - biosynthesis; Intermediate Filament Proteins - chemistry; Keratinocytes - metabolism; keratins; Keratins - metabolism; Medical sciences; periplakin; Plakins; Plectin; Poly(ADP-ribose) Polymerases - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Staurosporine - pharmacology; Time Factors; desmoplakin; Plectin; periplakin; Enzyme; Dermatology; Cysteine endopeptidases; Caspase; Desmosome; keratins; Protein; Peptidases; Keratin; Cell death; Hydrolases; caspases; Apoptosis
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.0906-6705.2004.00217.x

:  In epithelial cells, cell–cell and cell–matrix junctions, desmosomes and hemidesmosomes, provide anchorage sites for the keratin‐intermediate filaments. The plakin proteins desmoplakin (DP), plectin, and periplakin represent intracellular constituents of these adhesion junctions. In staurosporine‐treated apoptotic HaCaT cells, DP, plectin, and periplakin became cleaved coordinately with the elimination of keratins 10 and 14, while involucrin, actin, and keratin 18 displayed considerable stability. The caspase inhibitor zVAD‐fmk prevented both the cell detachment and protein cleavage, indicating the function of caspases in these events. Closer examination in vitro revealed that while caspases 2 and 4 most efficiently cleaved DP, and plectin served as a target for caspases 3 and 7, periplakin as well as keratins were cleaved by caspase 6. The involvement of multiple caspases in the destruction of epithelial cell integrity ensures the efficient elimination of cytoskeleton, but also provides specificity for selectively targeting individual adhesion molecules.