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. 2014 Jul 4;4:5573. doi: 10.1038/srep05573

Figure 8. The design principles of the ITUD system.

Figure 8

(a) Biphasic response of ITUD with respect to the perturbation on E3. (b) Possible mechanisms underlying the biphasicity of ITUD mediated by E3 ubiquitin ligases. (c) Possible regulatory mechanisms that affect the shapes of the biphasic response in the ITUD system (d) A representative example of a safety interlock device can be found in a clothes washing machine (left). The E3 ubiquitin ligase in the ITUD system can serve as a safety interlock device based on its integrated roles in proteolysis and transcription (right). (e) ITUD may support tissue homeostasis in multicellular organisms. (f) Combinatorial therapy based on ITUD. The relative output is the ratio of Pss between the inhibition of only T (single perturbation) and the inhibition of both T and E3 (dual perturbation) in the ITUD system. Perturbation strength is the percentage change of a kinetic parameter value to the perturbation of a system component, and the relative perturbation strength is the ratio between the single and dual perturbation strengths (see Methods for details).