Multiple Assembly Chaperones Govern Biogenesis of the Proteasome Regulatory Particle Base

Funakoshi, Mitsuaki; Tomko, Robert J.; Kobayashi, Hideki; Hochstrasser, Mark

doi:10.1016/j.cell.2009.04.061

Cited by 152 publications

(262 citation statements)

References 39 publications

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“…Our FCS analysis did not detect proteasome assembly intermediates in wild-type cells, probably because such intermediates are not abundant [37][38][39][40] . Previous studies using a specific importin-a mutant, srp1-49, suggested that nucleocytoplasmic transport mediated by importin a/b is coupled to proteasome biogenesis [19][20][21]23 .…”

Section: Resultsmentioning

confidence: 62%

Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome

et al. 2014

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The 26S proteasome is a 2.5-MDa multisubunit protease complex that degrades polyubiquitylated proteins. Although its functions and structure have been extensively characterized, little is known about its dynamics in living cells. Here, we investigate the absolute concentration, spatio-temporal dynamics and complex formation of the proteasome in living cells using fluorescence correlation spectroscopy. We find that the 26S proteasome complex is highly mobile, and that almost all proteasome subunits throughout the cell are stably incorporated into 26S proteasomes. The interaction between 19S and 20S particles is stable even in an importin-a mutant, suggesting that the 26S proteasome is assembled in the cytoplasm. Furthermore, a genetically stabilized 26S proteasome mutant is able to enter the nucleus. These results suggest that the 26S proteasome completes its assembly process in the cytoplasm and translocates into the nucleus through the nuclear pore complex as a holoenzyme.

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Section: Resultsmentioning

confidence: 62%

Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome

et al. 2014

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“…Two competing models exist for RP assembly ( Funakoshi et al , 2009; Le Tallec et al , 2009; Park et al , 2009; Roelofs et al , 2009). The first posits that RP assembly occurs in modules independent of the CP with the help of four RP-dedicated chaperones, named Hsm3, Nas2, Nas6 and Rpn14 ( Funakoshi et al , 2009).…”

Section: Discussion/analysis Of the Literaturementioning

confidence: 99%

“…The first posits that RP assembly occurs in modules independent of the CP with the help of four RP-dedicated chaperones, named Hsm3, Nas2, Nas6 and Rpn14 ( Funakoshi et al , 2009). In contrast, the second model proposes that the CP serves as a scaffold for the heterohexameric ATPase ring of the RP base ( Park et al , 2009).…”

Section: Discussion/analysis Of the Literaturementioning

confidence: 99%

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Chowdhury

Enenkel

2015

F1000Res

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The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus.Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body’s cells.

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“…Like the CP assembly pathway, the base assembly is also a highly organized process assisted by four base-dedicated chaperone proteins, including Nas2/p27, Nas6/gankyrin = p28, Rpn14/PAAF1, and Hsm3/S5b (yeast/human: miscellaneous nomenclature) (Funakoshi et al , 2009 ;Kaneko et al , 2009 ;Le Tallec et al , 2009 ;Park et al , 2009 ;Roelofs et al , 2009 ;Saeki et al , 2009 ). Recent studies proposed renaming of Rpn14, Nas6, Nas2, and Hsm3, to RP assembling chaperones (RACs), i.e., RAC1, 2, 3, and 4, respectively (Tomko and Hochstrasser , 2011 ).…”

Section: Deubiquitylating Enzymesmentioning

confidence: 99%

The proteasome: molecular machinery and pathophysiological roles

Tanaka

Mizushima

Saeki

2012

BCHM

108

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The 26S proteasome, in collaboration with ubiquitin, operates the energy-dependent regulated proteolysis process in eukaryotic cells. Over the past 30 years, several studies have comprehensively characterized the structure and molecular/ physiological functions of the 26S proteasome. It is a sophisticated 2.5-MDa protein degradation machine comprising a proteolytic core particle (CP) and one or two terminal regulatory particle(s) (RP). The CP consists of two outer α rings and two inner β rings, which are made up of seven structurally similar α and β subunits, respectively. The CP contains catalytic threonine residues ( β 1, β 2, and β 5; caspase-like, trypsin-like, and chymotrypsin-like activities, respectively) on the inner surface of the chamber formed by two abutting β rings. Intriguingly, the immunotype proteasomes, named ' immunoproteasome ' and ' thymoproteasome ' , whose catalytic subunits are replaced by the related counterparts, were discovered lately. Both unique isoenzymes essentially contribute to the acquisition of adaptive immunity in vertebrates. The RP, which serves to recognize polyubiquitylated substrate proteins and plays a role in their deubiquitylating, unfolding, and translocation into the interior of the CP for destruction, forms two subcomplexes: the base and the lid. On another front, the PA28 and PA200, alternative CP activator proteins discovered biochemically, both play independent roles in proteolysis of the 26S proteasome. Several studies have highlighted the importance of the proteasome in various intractable diseases that have been increasing in the aged society of the 21st century.

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Multiple Assembly Chaperones Govern Biogenesis of the Proteasome Regulatory Particle Base

Cited by 152 publications

References 39 publications

Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome

Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome

Intracellular Dynamics of the Ubiquitin-Proteasome-System

The proteasome: molecular machinery and pathophysiological roles

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