title: Degradation of ubiquitin: the fate of the cellular reaper.
abstract: Ubiquitin (Ub), a centrally important component of the ubiquitin-proteasome system (UPS), is covalently attached to numerous cellular proteins through a highly regulated process. The attached Ub serves as a recognition element in trans, to which a variety of downstream effectors bind. These complexes play roles in a broad array of cellular functions, the best studied is targeting of the conjugated proteins to degradation by the 26S proteasome. Regulated degradation plays key roles in basic processes such as cell cycle, differentiation, transcription, and maintenance of the cellular quality control. In addition to its conjugated form, there is also a free pool of Ub that is essential to ascertain its immediate availability for the many tasks it serves. Ub is considered as a stable protein, particularly due to its unique globular structure and ability to be recycled by deubiquitinating enzymes (DUBs). However, alterations in its steady state which occur under different pathophysiological conditions have suggested more complex, yet elusive, regulatory mechanisms that govern Ub stability. Recent findings have demonstrated that Ub can be degraded by the proteasome via three routes along with its conjugated substrate, when extended with a C-terminal tail, and as a monomer.
authors.affiliation: Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel. nshabek@tx.technion.ac.il
authors.forename: Nitzan
authors.initials: N
authors.lastname: Shabek
authors.forename: Aaron
authors.initials: A
authors.lastname: Ciechanover
mesh_terms: D000818:Animals; D004194:Disease; D006262:Health; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D025801:Ubiquitin