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Natural Substrates of the Proteasome and Their Recognition by the Ubiquitin System

  • Chapter
The Proteasome — Ubiquitin Protein Degradation Pathway

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 268))

Abstract

The 26S proteasome is recognized as the principal mediator of intracellular proteolysis in eukaryotes. As a consequence, its influence on cellular metabolism is as complex and manifold as are the proteins degraded by this protease, and new natural substrates are being discovered in ever increasing numbers. It has long been realized that the modulation of the steady-state levels of proteins can occur at the level of their synthesis as well as their degradation (Schimke 1973). Thus, one major area of proteasome function is the control of basic cellular processes such as cell cycle progression, signal transduction, and transcription via the degradation of short-lived regulatory factors. In addition, the proteasome plays a central role in the removal of misfolded, aberrant, or damaged proteins, which is a critical aspect of the cellular stress response. Last but not least, the mammalian proteasome is responsible for the generation of antigenic peptides presented on the cell surface by major histocompatibility complex (MHC) class I molecules as an integral part of the immune system (see the chapter by Niedermann, this volume). Tight control of proteasome activity is essential to guarantee the correctly timed removal of short-lived regulatory proteins but at the same time prevent the untimely destruction of other important cellular components not targeted for degradation. The system that distinguishes between stable proteins and those destined for breakdown and thus ensures the fidelity of selective proteolysis is the ubiquitin system. Accordingly, malfunctions or absence of components of this intricate enzymatic machinery lead to a variety of inherited or acquired diseases (Schwartz and Ciechanover 1999).

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  1. Department of Organismic Interactions, Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Strasse, 35043, Marburg/Lahn, Germany

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Ulrich, H.D. (2002). Natural Substrates of the Proteasome and Their Recognition by the Ubiquitin System. In: Zwickl, P., Baumeister, W. (eds) The Proteasome — Ubiquitin Protein Degradation Pathway. Current Topics in Microbiology and Immunology, vol 268. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59414-4_6

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