Nuclear translocation during the cross-talk between cellular stress, cell cycle and anticancer agents.

The function of many endogenous molecules in all eukaryotic cells depends on their subcellular localisation, being active when localized in one cellular compartment and inactive in another. Translocation or re-localization of mislocalized components in the optimal subcellular site may contribute to the development of novel cancer therapies and to the re-evaluation of conventional treatment. For instance, various agents are able to entrap cytoplasmic anti-apoptotic pathways to the nucleus, thus activating apoptosis. Moreover, amongst the factors identified so far, the optimal location of the tumor suppressor p53 for promoting cell arrest and apoptosis seems to be the nucleus, while the nuclear factor kappa B (NFkappaB) is desirable to stay in the cytoplasm. Thus, the mechanisms of nuclear translocation of endogenous signaling components, like p53, NFkappaB and various heat shock proteins (HSPs), may serve as targets for pharmacological intervention, without excluding the possible role of uptake and active transport into the nucleus of extracellular proteins.