Heterogeneous responses to low level death receptor activation are explained by random molecular assembly of the Caspase-8 activation platform.

ABSTRACT: Ligand binding to death receptors activates apoptosis in cancer cells. Stimulation of death receptors results in the formation of intracellular multiprotein platforms that either activate the apoptotic initiator Caspase-8 to trigger cell death, or signal through kinases to initiate inflammatory and cell survival signalling. Two of these platforms, the Death-Inducing Signalling Complex (DISC) and the RIPoptosome, also initiate necroptosis by building filamentous scaffolds that lead to the activation of mixed lineage kinase domain-like pseudokinase. To explain cell decision making downstream of death receptor activation, we developed a semi-stochastic model of DISC/RIPoptosome formation. The model is a hybrid of a direct Gillespie stochastic simulation algorithm for slow assembly of the RIPo

SUBMITTER: Matveeva A 

PROVIDER: S-EPMC6779275 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature