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Proposed model of the regulation of NFκB-dependent genes by proteasome inhibition in CTCL cells. Proteasome inhibition by BZ induces the nuclear translocation and accumulation of IκBα, which inhibits expression of NFκB p65/p50-regulated anti-apoptotic genes cIAP1 and cIAP2, resulting in the increased apoptosis of CTCL cells. In addition, the BZ-induced nuclear IκBα inhibits expression of TGFβ, which may decrease the immunosuppressive phenotype associated with advanced stages of CTCL.
