Details

Autor(en) / Beteiligte

• Schleich, Kolja
• Warnken, Uwe
• Fricker, Nicolai
• Öztürk, Selcen
• Richter, Petra
• Kammerer, Kerstin
• Schnölzer, Martina
• Krammer, Peter H.
• Lavrik, Inna N.

Titel

Stoichiometry of the CD95 Death-Inducing Signaling Complex: Experimental and Modeling Evidence for a Death Effector Domain Chain Model

Ist Teil von

• Molecular cell, 2012-07, Vol.47 (2), p.306-319

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The CD95 (Fas/APO-1) death-inducing signaling complex (DISC) is essential for the initiation of CD95-mediated apoptotic and nonapoptotic responses. The CD95 DISC comprises CD95, FADD, procaspase-8, procaspase-10, and c-FLIP proteins. Procaspase-8 and procaspase-10 are activated at the DISC, leading to the formation of active caspases and apoptosis initiation. In this study we analyzed the stoichiometry of the CD95 DISC. Using quantitative western blots, mass spectrometry, and mathematical modeling, we reveal that the amount of DED proteins procaspase-8/procaspase-10 and c-FLIP at the DISC exceeds that of FADD by several-fold. Furthermore, our findings imply that procaspase-8, procaspase-10, and c-FLIP could form DED chains at the DISC, enabling the formation of dimers and efficient activation of caspase-8. Taken together, our findings provide an enhanced understanding of caspase-8 activation and initiation of apoptosis at the DISC. [Display omitted] ► The amount of procaspase-8/procaspase-10 and c-FLIP at the DISC exceeds that of FADD ► Procaspase-8, procaspase-10, and c-FLIP could form DED chains/platforms at the DISC, ► The length of the DED chains is variable and depends on the stimulation strength ► Mathematical model supported by quantitative mass spectrometry and western blot