Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosis

• Verfasst von: Stegh, Alexander H. [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Verfasst von: Peter, Marcus E. [VerfasserIn]
• Titel: Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosis
• Verf.angabe: Alexander H. Stegh, Harald Herrmann, Stefan Lampel, Dieter Weisenberger, Kerstin Andrä, Martin Seper, Gerhard Wiche, Peter H. Krammer, and Marcus E. Peter
• E-Jahr: 2000
• Jahr: August 1, 2000
• Umfang: 15 S.
• Teil: volume:20
• Teil: year:2000
• Teil: number:15
• Teil: pages:5665-5679
• Teil: extent:15
• Fussnoten: Gesehen am 26.04.2021
• Titel Quelle: Enthalten in: Molecular and cellular biology
• Ort Quelle: Washington, DC : Soc., 1981
• Jahr Quelle: 2000
• Band/Heft Quelle: 20(2000), 15, Seite 5665-5679
• ISSN Quelle: 1098-5549
• DOI: doi:10.1128/MCB.20.15.5665-5679.2000
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1755942389

Abstract

Caspase 8 plays an essential role in the execution of death receptor-mediated apoptosis. To determine the localization of endogenous caspase 8, we used a panel of subunit-specific anti-caspase 8 monoclonal antibodies in confocal immunofluorescence microscopy. In the human breast carcinoma cell line MCF7, caspase 8 predominantly colocalized with and bound to mitochondria. After induction of apoptosis through CD95 or tumor necrosis factor receptor I, active caspase 8 translocated to plectin, a major cross-linking protein of the three main cytoplasmic filament systems, whereas the caspase 8 prodomain remained bound to mitochondria. Plectin was quantitatively cleaved by caspase 8 at Asp 2395 in the center of the molecule in all cells tested. Cleavage of plectin clearly preceded that of other caspase substrates such as poly(ADP-ribose) polymerase, gelsolin, cytokeratins, or lamin B. In primary fibroblasts from plectin-deficient mice, apoptosis-induced reorganization of the actin cytoskeleton, as seen in wild-type cells, was severely impaired, suggesting that during apoptosis, plectin is required for the reorganization of the microfilament system.