The immunoproteasome and thymoproteasome: functions, evolution and human disease

Murata, Shigeo; Takahama, Yousuke; Kasahara, Masanori; Tanaka, Keiji

doi:10.1038/s41590-018-0186-z

Cited by 235 publications

(209 citation statements)

References 122 publications

Supporting

Mentioning

203

Contrasting

Unclassified

Order By: Relevance

“…Therefore, immunoproteasomes enhance ligand generation for MHC Class I molecules, allowing for surveillance by CD8 + T lymphocytes. Immunoproteasome formation following cytokine induction is rapid, cooperative, and can be transient [72][73][74]. Originally thought to be strictly involved in antigen presentation, immunoproteasomes have also been implicated in other cellular processes, including T cell polarization and cytokine production by macrophages [66].…”

Section: Immunoproteasomementioning

confidence: 99%

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease

Sherman

Li²

2020

Molecules

View full text Add to dashboard Cite

The proteasome is the central component of the main cellular protein degradation pathway. During the past four decades, the critical function of the proteasome in numerous physiological processes has been revealed, and proteasome activity has been linked to various human diseases. The proteasome prevents the accumulation of misfolded proteins, controls the cell cycle, and regulates the immune response, to name a few important roles for this macromolecular “machine.” As a therapeutic target, proteasome inhibitors have been approved for the treatment of multiple myeloma and mantle cell lymphoma. However, inability to sufficiently inhibit proteasome activity at tolerated doses has hampered efforts to expand the scope of proteasome inhibitor-based therapies. With emerging new modalities in myeloma, it might seem challenging to develop additional proteasome-based therapies. However, the constant development of new applications for proteasome inhibitors and deeper insights into the intricacies of protein homeostasis suggest that proteasome inhibitors might have novel therapeutic applications. Herein, we summarize the latest advances in proteasome inhibitor development and discuss the future of proteasome inhibitors and other proteasome-based therapies in combating human diseases.

show abstract

Section: Immunoproteasomementioning

confidence: 99%

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease

Sherman

Li²

2020

Molecules

View full text Add to dashboard Cite

show abstract

“…The immunosubunits display structural homologies to the standard proteasome (SP) subunits. Proteasome isoforms containing these immunosubunits are called immunoproteasome (IP) (Figure 2), [34][35][36][37][38][39][40][41] which are constitutively expressed in cells of myeloid or lymphoid origin. 42 Immunoproteasome subunits are preferentially incorporated into newly synthesized proteasome complexes by a selective assembly mechanism.…”

Section: Protein Deg R Adati On By Prote a Some Comple Xe Smentioning

confidence: 99%

Structure and function of the ubiquitin‐proteasome system in platelets

Colberg

Cammann

Greinacher

et al. 2020

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Platelets are small anucleate blood cells with a life span of 7 to 10 days. They are main regulators of hemostasis. Balanced platelet activity is crucial to prevent bleeding or occlusive thrombus formation. Growing evidence supports that platelets also participate in immune reactions, and interaction between platelets and leukocytes contributes to both thrombosis and inflammation. The ubiquitin‐proteasome system (UPS) plays a key role in maintaining cellular protein homeostasis by its ability to degrade non‐functional self‐, foreign, or short‐lived regulatory proteins. Platelets express standard and immunoproteasomes. Inhibition of the proteasome impairs platelet production and platelet function. Platelets also express major histocompatibility complex (MHC) class I molecules. Peptide fragments released by proteasomes can bind to MHC class I, which makes it also likely that platelets can activate epitope specific cytotoxic T lymphocytes (CTLs). In this review, we focus on current knowledge on the significance of the proteasome for the functions of platelets as critical regulators of hemostasis as well as modulators of the immune response.

show abstract

“…In its mixed α 7 β 7 β 7 α 7 architecture, only the β rings are catalytically active, and in eukaryotes, where both ring types are composed of seven different subunits, only three of the β subunits are active, each of them possessing another proteolytic specificity . Moreover, in organisms with adaptive immunity, cell‐type specific immunosubunits can replace regular β subunits to form an immunoproteasome . This distinctive modularity within the eukaryotic 20S proteasome is conceivably facilitated by the presence of the α rings as assembly scaffolds—it is not paralleled by the other members of the proteasome family, which merely form a double ring of identical subunits.…”

Section: Members Of the Proteasome Family Differ In Their Functional mentioning

confidence: 99%

“…[27] Moreover, in organisms with adaptive immunity, cell-type specific immunosubunits can replace regular β subunits to form an immunoproteasome. [28] This distinctive modularity within the eukaryotic 20S proteasome is conceivably facilitated by the presence of the α rings as assembly scaffolds-it is not paralleled by the other members of the proteasome family, which merely form a double ring of identical subunits.…”

Section: Members Of the Proteasome Family Differ In Their Functional mentioning

confidence: 99%

On the Origins of Symmetry and Modularity in the Proteasome Family

Fuchs

Hartmann

2019

BioEssays

View full text Add to dashboard Cite

The proteasome family of proteases comprises oligomeric assemblies of very different symmetry. In different sizes, it features ring‐like oligomers with dihedral symmetry that allow the stacking of further rings of regulatory subunits as observed in the modular proteasome system, but also less symmetric helical assemblies. Comprehensive sequence and structural analyses of proteasome homologs reveal a parsimonious scenario of how symmetry may have emerged from a monomeric ancestral precursor and how it may have evolved throughout the proteasome family. The four characterized representatives—ancestral β subunit (Anbu), HslV, betaproteobacterial proteasome homolog (BPH), and the 20S proteasome—are outlasting cornerstones in the family's evolutionary history, each marking a transition in symmetry. This article contextualizes the evolutionary and functional key aspects of these symmetry transitions, explaining how they facilitated the diversification and concurrent evolution of independent proteolytic systems side by side, each with its customized network of auxiliary interactors.

show abstract

The immunoproteasome and thymoproteasome: functions, evolution and human disease

Cited by 235 publications

References 122 publications

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease

Structure and function of the ubiquitin‐proteasome system in platelets

On the Origins of Symmetry and Modularity in the Proteasome Family

Contact Info

Product

Resources

About