The ubiquitin proteasome system (UPS) regulates perhaps the most intriguing balance in all of biology: how cells control protein function and malfunction in order to regulate, and eventually eliminate, the old and error prone while simultaneously synthesizing and orchestrating the new. In light of the growing notion that ubiquitination and the 26S proteasome are central to a multiplicity of diverse cellular functions, we discuss here the proteolytic and non-proteolytic roles of the UPS in regulating pathways ultimately involved in protein synthesis and activity including roles in epigenetics, transcription, and post-translational modifications. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!
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