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Bell J.E.,Institute for Structural Biology and Drug Discovery | Bell J.K.,Center for the Study of Biological Complexity | Bell J.K.,Virginia Commonwealth University | Bell J.K.,University of Richmond
Journal of Biological Chemistry | Year: 2013

Background: Suppressor of IkB kinase (SIKE) inhibits a key innate immune effector molecule, TANK-binding kinase 1 (TBK1), through an undefined mechanism. Results: SIKE is a TBK1 substrate. Conclusion: SIKE controls TBK1 activity by acting as a high affinity substrate. Significance: SIKE attenuates phosphorylation of interferon regulatory factor 3 (IRF3) by serving as an alternative, high affinity substrate for TBK1. © 2013 by The American Society.

Apte A.,Virginia Commonwealth University | Bonchev D.,Center for the Study of Biological Complexity | Bonchev D.,Virginia Commonwealth University | Fong S.,Virginia Commonwealth University | Fong S.,Center for the Study of Biological Complexity
Chemistry and Biodiversity | Year: 2010

Two strategies for fighting cancer by modulating FASL-induced apoptosis were modeled by 2D-cellular automata. Our models predict that cancer cells can be killed by maximizing the apoptosis via joint suppression of FLIP and IAP inhibitors by siRNA and SMAC proteins, respectively. It was also predicted that the presumed feedback loop CASP3→CASP9→|IAP in the intrinsic pathway accelerates the apoptosis, but does not change significantly the concentration of DFF40, the protein that decomposes DNA. The alternative strategy of preventing the killing of the immune system's T-cells, via minimizing their tumor-induced FAS-L apoptosis by overexpression of FLIP and IAP, was also shown to be promising with a predicted considerable synergy action of the two inhibitors. Dual suppression or overexpression of apoptosis inhibitors emerges thus as promising approach in the fight against cancer. Our modeling has also brought some light on the process of turning type-I cells into type-II ones, which emerges as compensatory mechanism in case of damaged or silenced FASL pathway by preserving about the same self-death level at only 10-12% lower performance rate. © 2010 Verlag Helvetica Chimica Acta AG.

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