Figure 6From: The proteosome inhibitor MG132 attenuates Retinoic Acid Receptor trans-activation and enhances trans-repression of Nuclear Factor κB. Potential relevance to chemo-preventive interventions with retinoidsA reductionist model for optimizing the anticancer property of retinoids. The classical IκB-NFκB signaling cascade proceeds through the sequential phosphorylation, ubiquitination (ub) and proteosomal degradation of IκBα and the coordinate release and nuclear translocation of NFκB. Hyper-activation of NFκB in cancer can be overridden by hyper-activating RAR with retinoids. As such retinoid therapy induces malignant reversion but is associated with retinoid toxicity. Proteosome inhibitors quell RAR trans-activation and enhance RAR trans-repression of NFκB.Back to article page