[HTML][HTML] Structure, dynamics and function of the 26S proteasome

Y Mao - Macromolecular protein complexes III: structure and …, 2021 - Springer
The 26S proteasome is the most complex ATP-dependent protease machinery, of~ 2.5 MDa
mass, ubiquitously found in all eukaryotes. It selectively degrades ubiquitin-conjugated …

Proteasome substrate receptors and their therapeutic potential

V Osei-Amponsa, KJ Walters - Trends in biochemical sciences, 2022 - cell.com
The ubiquitin-proteasome system (UPS) is critical for protein quality control and regulating
protein lifespans. Following ubiquitination, UPS substrates bind multidomain receptors that …

Proteasome interaction with ubiquitinated substrates: from mechanisms to therapies

X Chen, ZM Htet, E López‐Alfonzo, A Martin… - The FEBS …, 2021 - Wiley Online Library
The 26S proteasome is responsible for regulated proteolysis in eukaryotic cells. Its
substrates are diverse in structure, function, sequence length, and amino acid composition …

[HTML][HTML] hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-κB p50

V Osei-Amponsa, M Chandravanshi, X Lu, V Magidson… - Molecular Cell, 2024 - cell.com
The anti-cancer target hRpn13 is a proteasome substrate receptor. However, hRpn13-
targeting molecules do not impair its interaction with proteasomes or ubiquitin, suggesting …

Mechanisms of substrate recognition by the 26S proteasome

C Davis, BL Spaller, A Matouschek - Current opinion in structural biology, 2021 - Elsevier
Highlights•Many types of ubiquitin modification can target proteins to the proteasome for
degradation.•The ubiquitin receptors of the RP individually and cooperatively function to …

Branched ubiquitin chain binding and deubiquitination by UCH37 facilitate proteasome clearance of stress-induced inclusions

A Song, Z Hazlett, D Abeykoon, J Dortch, A Dillon… - Elife, 2021 - elifesciences.org
UCH37, also known as UCHL5, is a highly conserved deubiquitinating enzyme (DUB) that
associates with the 26S proteasome. Recently, it was reported that UCH37 activity is …

[HTML][HTML] Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma

X Lu, VR Sabbasani, V Osei-Amponsa… - Nature …, 2021 - nature.com
Proteasome substrate receptor hRpn13 is a promising anti-cancer target. By integrated in
silico and biophysical screening, we identified a chemical scaffold that binds hRpn13 with …

[HTML][HTML] Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2

SAA Rehman, LA Armstrong, SM Lange… - Molecular cell, 2021 - cell.com
Of the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-
linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins …

[HTML][HTML] A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins

X Lu, M Chandravanshi, VR Sabbasani… - Nature …, 2024 - nature.com
Proteasome subunit hRpn13 is partially proteolyzed in certain cancer cell types to generate
hRpn13Pru by degradation of its UCHL5/Uch37-binding DEUBAD domain and retention of …

[HTML][HTML] Proteasome inhibition is an effective treatment strategy for microsporidia infection in honey bees

EM Huntsman, RM Cho, HV Kogan… - Biomolecules, 2021 - mdpi.com
The microsporidia Nosema ceranae is an obligate intracellular parasite that causes honey
bee mortality and contributes to colony collapse. Fumagillin is presently the only …