The proteasome: a protein‐destroying machine

Abstract

Most cellular proteins are targeted for degradation by the proteasome, a eukaryotic ATPdependent 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.

Herp, a New Ubiquitin-like Membrane Protein Induced by Endoplasmic Reticulum Stress

“…Many proteins with a structural similarity to ubiquitin present in cells, Ubls (ubiquitin-like proteins), are divided into two subclasses: small, type-1 Ubls, such as SUMO-1 and NEDD8, that are ligated to target proteins in a similar manner to ubiquitin, and type-2 Ubls containing ubiquitin-like structures within a variety of large proteins having distinct functions, such as Elongin B, Rad23, and Parkin. Although ubiquitin and type-1 Ubls are central players in post-translational protein modification, the significance of type-2 Ubls remains obscure (42,43). The lack of a diglycine motif at the C-terminal end of the ubiquitin domain suggests that Herp is a type-2 Ubl.…”

Reactivity of Anti-Proliferating Cell Nuclear Antigen (PCNA) Murine Monoclonal Antibodies and Human Autoantibodies to the PCNA Multiprotein Complexes Involved in Cell Proliferation

“…Other candidates that may interact with PCNA are proteins associated with the ubiquitin-proteasome pathway (50). Proteasome was originally described as a holoenzyme playing an important role in the production of peptides presented by MHC class I molecules (50), but recent studies have revealed proteasome to be involved in cell cycle regulation and to bind to cyclin B, cyclin D, p21, CDK 5, and p27, all of which interact with PCNA (50 -53).…”

Solution Structure of the Kaposi's Sarcoma-associated Herpesvirus K3 N-terminal Domain Reveals a Novel E2-binding C4HC3-type RING Domain

“…Ubiquitination was originally characterized as a signal for protein destruction by the proteasome (1). However, recent developments have implicated ubiquitin in control of a multitude of cellular processes including signal transduction, apoptosis, DNA repair, protein-protein interaction, endocytosis, and protein trafficking (2)(3)(4).…”