Human SV80 Cells: Control vs. Caspase-8 knock down

Excessive responses to pattern-recognition receptors are prevented by regulatory mechanisms that affect the amounts, conformation, and associative properties of their signaling proteins. We report that signaling by the ribonucleic acid sensor RIG-I is restricted, in addition, by caspase-mediated cleavage that results in conversion of a signaling enhancer to a signaling inhibitor. RIP1 and caspase-8, two proteins known to mediate effects of receptors of the TNF/NGF family, are recruited to the RIG-I complex following viral infection, and serve in a coordinated manner antagonistic regulatory roles: conjugation of a ubiquitin chain to Lys-377 in RIP1 facilitates assembly of the RIG-I complex, but it also renders RIP1 susceptible to caspase-8-mediated cleavage, yielding an inhibitory RIP1 fragment. The dependence of RIP1 cleavage on the same molecular change as the one that facilitates RIG-I signaling allows for RIG-I signaling to be restricted in its duration without compromising its initial activation. Transcriptional profiling of human SV80 cells comparing cells infected with control lenti virus to cells infected with caspase-8 siRNA expressing lenti virus. Goal was to determine the effects of caspase-8 knock down on global gene expression. Two-condition experiment, Control lenti Vs caspase-8 siRNA expressing lenti. Biological replicates: 4 control, 4 caspase-8 siRNA infected