Most cellular proteins are targeted for degradation by the proteasome, a eukaryotic ATP-dependent protease, after they have been covalently attached to ubiquitin (Ub) in the form of a poly Ub chain functioning as a degradation signal. The proteasome is an unusually large multisubunit proteolytic complex, consisting of a central catalytic machine (called the 20S proteasome) and two terminal regulatory subcomplexes, termed PA700 or PA28, that are attached to both ends of the central portion in opposite orientations, to form enzymatically active proteasomes. The large assembled proteasome acts as a protein-destroying machine responsible for the selective breakdown of numerous ubiquitinylated cellular proteins and certain nonubiquitinylated proteins. To date, proteolysis mediated by the Ub-proteasome pathway has been shown to be involved in a wide variety of biologically important processes, such as the cell cycle, apoptosis, metabolism, signal transduction, immune response and protein quality control, implying that it functions as a previously unrecognized regulatory system for determining the final fate of protein factors involved in these biological reactions.

This article has been cited by other articles:

				W. Yang, L. Chen, Y. Ding, X. Zhuang, and U. J. Kang Paraquat induces dopaminergic dysfunction and proteasome impairment in DJ-1-deficient mice Hum. Mol. Genet., December 1, 2007; 16(23): 2900 - 2910. [Abstract] [Full Text] [PDF]

				M. Yamashita, R. Shinnakasu, H. Asou, M. Kimura, A. Hasegawa, K. Hashimoto, N. Hatano, M. Ogata, and T. Nakayama Ras-ERK MAPK Cascade Regulates GATA3 Stability and Th2 Differentiation through Ubiquitin-Proteasome Pathway J. Biol. Chem., August 19, 2005; 280(33): 29409 - 29419. [Abstract] [Full Text] [PDF]

				H. Usami, Y. Kusano, T. Kumagai, S. Osada, K. Itoh, A. Kobayashi, M. Yamamoto, and K. Uchida Selective Induction of the Tumor Marker Glutathione S-Transferase P1 by Proteasome Inhibitors J. Biol. Chem., July 1, 2005; 280(26): 25267 - 25276. [Abstract] [Full Text] [PDF]

				R. B. Dodd, M. D. Allen, S. E. Brown, C. M. Sanderson, L. M. Duncan, P. J. Lehner, M. Bycroft, and R. J. Read Solution Structure of the Kaposi's Sarcoma-associated Herpesvirus K3 N-terminal Domain Reveals a Novel E2-binding C4HC3-type RING Domain J. Biol. Chem., December 17, 2004; 279(51): 53840 - 53847. [Abstract] [Full Text] [PDF]

				Y. Ogiso, A. Tomida, and T. Tsuruo Nuclear Localization of Proteasomes Participates in Stress-inducible Resistance of Solid Tumor Cells to Topoisomerase II-directed Drugs Cancer Res., September 1, 2002; 62(17): 5008 - 5012. [Abstract] [Full Text] [PDF]

				D. Ungureanu, P. Saharinen, I. Junttila, D. J. Hilton, and O. Silvennoinen Regulation of Jak2 through the Ubiquitin-Proteasome Pathway Involves Phosphorylation of Jak2 on Y1007 and Interaction with SOCS-1 Mol. Cell. Biol., May 15, 2002; 22(10): 3316 - 3326. [Abstract] [Full Text] [PDF]

				Y. Takasaki, T. Kogure, K. Takeuchi, K. Kaneda, T. Yano, K. Hirokawa, S. Hirose, T. Shirai, and H. Hashimoto Reactivity of Anti-Proliferating Cell Nuclear Antigen (PCNA) Murine Monoclonal Antibodies and Human Autoantibodies to the PCNA Multiprotein Complexes Involved in Cell Proliferation J. Immunol., April 1, 2001; 166(7): 4780 - 4787. [Abstract] [Full Text] [PDF]