The role of the ubiquitin-proteasome pathway in skin cancer development: 26S proteasome-activated NF-κB signal transduction.

The Ubiquitin-Proteasome System plays a central role in signal transduction associated with stress, in the skin in particular by the control of NF-κB pathways. Under normal conditions, the inhibitory protein IκB is phosphorylated by kinases, then ubiquitinated and ends up at the proteasome to be degraded. The present short review discusses recent progress in the inhibition of NF-κB activation by proteasome inhibitors prevents the degradation of protein IκB, which accumulates in the cytosol, and there by the activation of NF-κB. Moreover, would not only limit the expression of adhesion molecules and cytokines involved in metastatic processes, but also increase the sensitivity of cancer cells to apoptosis. Considering this fact, the activity of NF-κB is regulated by the phosphorylation and proteasome-dependent degradation of its inhibitor Iκb. In this scenario, the use of a proteasome inhibitor might be an effective strategy in the treatment of skin cancer with constitutive activation of NF-κB.