ReviewIlluminating the ubiquitin/proteasome system
Section snippets
General introduction
Proteolysis is crucial for maintaining the quality of the cellular proteome. Among the various proteolytic systems in eukaryotic cells, the ubiquitin/proteasome system (UPS) is responsible for the controlled processive degradation of proteins residing in the nucleus, cytosol, and endoplasmic reticulum. This requires the coordinated actions of a large number of proteins that are involved successively in the recognition of substrates, the tagging of substrates with poly-ubiquitin chains, and the
Fluorescent ubiquitin
Covalent linkage of the C terminus of ubiquitin to a lysine residue in substrates, a process known as ubiquitylation, has a central regulatory role in a variety of cellular mechanisms. Besides its canonical role in targeting proteins for proteasomal degradation, ubiquitylation can also change the fate of a protein in very different ways. Non-proteolytic functions of ubiquitin are important in, for example, chromatin remodeling, DNA repair, endocytosis, signal transduction, and transcription [6]
Fluorescent proteasome
The 26S proteasome is a large proteolytic complex consisting of a 20S core particle and one or two 19S regulatory particles (Fig. 2A). The 20S core particle consists of four rings, each containing seven subunits. For simplicity, we will use throughout this review the unified nomenclature for the proteasome subunits [3], [27]. Each of the two outer rings is composed of seven unique α subunits, while the two inner rings each consist of seven unique β subunits [28] (Fig. 2B). The proteolytic
Concluding remarks
Fluorescent labeling of UPS components has given a deeper understanding of the behavior of this proteolytic system in living cells. The recent development of new fluorescent techniques and the generation of new fluorescent proteins, such as proteins that undergo photoconversion after exposure to light with a specific wavelength, like PAGFP [42] and mOrange [43], will further increase the power of live cell imaging in studies on the UPS. The progress in automated microscopy and data analysis can
Acknowledgments
The research in the Dantuma laboratory is supported by the Swedish Research Council, the Swedish Cancer Society, the Nordic Center of Excellence Neurodegeneration, and the European Community Network of Excellence RUBICON (Project no LSHC-CT-2005-018683).
References (47)
The development of proteasome inhibitors as anticancer drugs
Cancer Cell
(2004)- et al.
Ubiquitin: not just for proteasomes anymore
Curr. Opin. Cell Biol.
(2003) - et al.
Polyubiquitin chains: polymeric protein signals
Curr. Opin. Chem. Biol.
(2004) - et al.
Final stages of cytokinesis and midbody ring formation are controlled by BRUCE
Cell
(2008) - et al.
Fusion proteins with COOH-terminal ubiquitin are stable and maintain dual functionality in vivo
J. Biol. Chem.
(2002) - et al.
Conformational disease
Lancet
(1997) - et al.
Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases
Neuron
(2001) - et al.
The ubiquitin proteasome system in neuordegenerative diseases: sometimes the chicken, sometimes the egg
Neuron
(2003) - et al.
RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins
Cell
(2007) - et al.
Unified nomenclature for subunits of the Saccharomyces cerevisiae proteasome regulatory particle
Trends Biochem. Sci.
(1998)
The proteasome: paradigm of a self-compartmentalizing protease
Cell
Rpn5 is a conserved proteasome subunit and required for proper proteasome localization and assembly
J. Biol. Chem.
Schizosaccharomyces pombe Int6 and Ras homologs regulate cell division and mitotic fidelity via the proteasome
Cell
A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo
Chem. Biol.
The ubiquitin system
Annu. Rev. Biochem.
Mechanisms underlying ubiquitination
Annu. Rev. Biochem.
Recognition and processing of ubiquitin–protein conjugates by the proteasome
Annu. Rev. Biochem.
The ubiquitin–proteasome pathway and pathogenesis of human diseases
Annu. Rev. Med.
Protein regulation by monoubiquitin
Nat. Rev. Mol. Cell Biol.
Ubiquitin-binding domains—from structures to functions
Nat. Rev. Mol. Cell Biol.
Intranuclear ataxin1 inclusions contain both fast- and slow-exchanging components
Nat. Cell Biol.
Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome
J. Cell Biol.
Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins
J. Cell Biol.
Cited by (31)
Intracellular localization of the proteasome in response to stress conditions
2022, Journal of Biological ChemistryCitation Excerpt :In contrast to these studies, proteasomal antibodies such as MCP444 (anti-PSMB7 CP β7), which coimmunoprecipitate proteasome holoenzymes, yielded a major nuclear proteasome localization in HeLa, COS-7, U2OS, and KOLF cells, as shown by datasheets of different commercial providers (and our unpublished results). In parallel, a CP α3 subunit fusion with the GFP is suitable as proteasomal reporter in direct fluorescence microscopy and revealed a nuclear localization in HeLa and MelJuSo cells (36, 37). The predominant proteasome localization in the nucleus of mammalian cells was unexpected, as cytoplasmic localization had been the prevailing paradigm.
Using the ubiquitin-modified proteome to monitor distinct and spatially restricted protein homeostasis dysfunction
2016, Molecular and Cellular ProteomicsRosiglitazone activation of PPARγ-dependent signaling is neuroprotective in mutant huntingtin expressing cells
2015, Experimental Cell ResearchThe role of the F-box gene TaFBA1 from wheat (Triticum aestivum L.) in drought tolerance
2014, Plant Physiology and Biochemistry