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 …

Development of a novel PROTAC using the nucleic acid aptamer as a targeting ligand for tumor selective degradation of nucleolin

L Zhang, L Li, X Wang, H Liu, Y Zhang, T Xie… - … Therapy-Nucleic Acids, 2022 - cell.com
PROteolysis TArgeting Chimeras (PROTACs) induce targeted protein degradation by
hijacking the intracellular ubiquitin proteasome system, thus emerging as a new strategy for …

[HTML][HTML] Autism-linked UBE3A gain-of-function mutation causes interneuron and behavioral phenotypes when inherited maternally or paternally in mice

L Xing, JM Simon, TS Ptacek, JY Jason, L Loo, H Mao… - Cell reports, 2023 - cell.com
The E3 ubiquitin ligase Ube3a is biallelically expressed in neural progenitors and glial cells,
suggesting that UBE3A gain-of-function mutations might cause neurodevelopmental …

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 …

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 …

E6AP AZUL interaction with UBQLN1/2 in cells, condensates, and an AlphaFold-NMR integrated structure

GR Buel, X Chen, W Myint, O Kayode, V Folimonova… - Structure, 2023 - cell.com
Summary The E3 ligase E6AP/UBE3A has a dedicated binding site in the 26S proteasome
provided by the RAZUL domain of substrate receptor hRpn10/S5a/PSMD4. Guided by …

[HTML][HTML] Exploration of aberrant E3 ligases implicated in Alzheimer's disease and development of chemical tools to modulate their function

FM Potjewyd, AD Axtman - Frontiers in Cellular Neuroscience, 2021 - frontiersin.org
The Ubiquitin Proteasome System (UPS) is responsible for the degradation of misfolded or
aggregated proteins via a multistep ATP-dependent proteolytic mechanism. This process …

Exploring the “Other” subfamily of HECT E3-ligases for therapeutic intervention

S Singh, J Ng, J Sivaraman - Pharmacology & Therapeutics, 2021 - Elsevier
The HECT E3 ligase family regulates key cellular signaling pathways, with its 28 members
divided into three subfamilies: NEDD4 subfamily (9 members), HERC subfamily (6 …

Discovery of reactive peptide inhibitors of human papillomavirus oncoprotein E6

X Ye, P Zhang, J Tao, JCK Wang, A Mafi, NM Grob… - Chemical …, 2023 - pubs.rsc.org
Human papillomavirus (HPV) infections account for nearly all cervical cancer cases, which is
the fourth most common cancer in women worldwide. High-risk variants, including HPV16 …