The proteasomal system

Abstract

Rising interest in the mechanism and function of the proteasomes and the ubiquitin system revealed that it is hard to find any aspect of the cellular metabolic network that is not directly or indirectly affected by the degradation system. This includes the cell cycle, the "quality control" of newly synthesized proteins (ERAD), transcription factor regulation, gene expression, cell differentiation, immune response or pathologic processes like cancer, neurodegenerative diseases, lipofuscin formation, diabetes, atherosclerosis, inflammatory processes or cataract formation and in addition to that the aging process itself and the degradation of oxidized proteins, in order to maintain cell homeostasis. But also this seems to be only a small aspect of the general view. The various regulator proteins that are able to change the rate or specificity of proteolysis, fitting it out for highly specialized tasks, or the precise regulation of the half-life of cellular proteins by ubiquitin-mediated degradation shape the proteasome and the ubiquitin-proteasome system into a fascinating and essential part of cellular function in the three kingdoms of bacteria, plants and animals. This review tries to summarize the current knowledge on the proteasome and the ubiquitin-proteasomal system, including the cellular functions of this system.