NFκB function and regulation in cutaneous T-cell lymphoma.

The nuclear accumulation and transcriptional activity of NFκB are constitutively increased in cutaneous T-cell lymphoma (CTCL) cells, and are responsible for their increased survival and proliferation. However, in addition to the anti-apoptotic and pro-inflammatory genes, NFκB induces expression of immunosuppressive genes, such as IL-10 and TGFβ, which inhibit the immune responses and are characteristic for the advanced stages of CTCL. While the mechanisms regulating NFκB-dependent transcription of anti-apoptotic and pro-inflammatory genes have been studied extensively, very little is known about the NFκB regulation of immunosuppressive genes. The specificity of NFκB-regulated responses is determined by the subunit composition of NFκB complexes recruited to the individual promoters, post-translational modifications of NFκB proteins, as well as by their interactions with other transcriptional factors and regulators. In this review, we discuss the mechanisms regulating the transcription of NFκB-dependent anti-apoptotic, pro-inflammatory and immunosuppressive genes in CTCL cells, as potential targets for CTCL therapies.