Immunologic aspects of protein degradation by the ubiquitin-proteasome system.

The ubiquitin-proteasome pahtway has a central ? in selective degradation of intracellular proteins Among the key proteins degraded by the system are those involved in the control of inflammation and cycle regulation and gene expression. With namerous importane cellular pathways affected, derangements in the ubiquitin system were shown to result in a variety of human diseases including malignancies neurodegenerative diseases and hereditary syndromes, and protea-some inhibition was implicated as a potential treatment for cancer and inflammatory conditions Two proteasome inhibitors are currently under clinical evaluation for multiple myeloma and acute ischemic stroke. The ubiquitin system also has an important function in the immune and inflammatory response it is involved in antigen processing and presentation to cytotoxic T cells and the activation of nuclear facter kappa B - the central transcription factor of the immune system. Since the proteasome is the central source of antigenic peptioes that are presented to the immune system some viruses. such as the Epstein Barr virus developed escape mechanisms that manipulate the ubiquitin-proteasome system in order to persist in the infected host Understanding the mechanisms inderlying the production of viral antigens by the ubiquitin-proteasome system may have therapeutic applications such as future development of vaccines.