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Verfasst von:Kallenberger, Stefan M. [VerfasserIn]   i
 Beaudouin, Joël [VerfasserIn]   i
 Claus, Juliane [VerfasserIn]   i
 Eils, Roland [VerfasserIn]   i
Titel:Intra- and interdimeric caspase-8 self-cleavage controls strength and timing of CD95-induced apoptosis
Verf.angabe:Stefan M. Kallenberger, Joël Beaudouin, Juliane Claus, Carmen Fischer, Peter K. Sorger, Stefan Legewie, and Roland Eils
E-Jahr:2014
Jahr:11 Mar 2014
Umfang:? S.
Fussnoten:Gesehen am 06.08.2020
Titel Quelle:Enthalten in: Science signaling
Ort Quelle:Washington, DC [u.a.] : Assoc., 2008
Jahr Quelle:2014
Band/Heft Quelle:7(2014,316) Artikel-Nummer ra23, 33 Seiten
ISSN Quelle:1937-9145
Abstract:Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis. - Dual modes of activation of caspase-8 enable precise control of apoptosis. - Dual modes of activation of caspase-8 enable precise control of apoptosis.
DOI:doi:10.1126/scisignal.2004738
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1126/scisignal.2004738
 Volltext ; Verlag: https://stke.sciencemag.org/content/7/316/ra23
 Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208692/pdf/nihms627852.pdf
 DOI: https://doi.org/10.1126/scisignal.2004738
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1726534685
Verknüpfungen:→ Zeitschrift

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