Cellular Responses to Proteasome Impairment

A functional ubiquitin-proteasome system (UPS) is essential for all eukaryotic cells. It serves qualitative and quantitative roles within the cellular proteome as it specifically targets misfolded or otherwise damaged proteins for destruction and hence prevents aggregation and accumulation of cytotoxic products. Moreover, many regulatory proteins such as transcription factors, cell cycle regulators, DNA replication and DNA repair proteins are selectively targeted for degradation via proteasome complexes which thus contribute to the regulation of various intracellular pathways. Consequently, any kind of insufficient capacity of proteasome-mediated protein degradation can result in proteotoxic stress and as such to have a serious effect on the entire cellular homeostasis. This chapter discusses the major causes of proteasome and UPS impairment and its impact on cellular signaling pathways. It also provides an overview of the current understanding of the potential crosstalk between disturbed proteasome activity and inflammatory signaling pathways.