Modulating biomolecular condensates: a novel approach to drug discovery

DM Mitrea, M Mittasch, BF Gomes, IA Klein… - Nature Reviews Drug …, 2022 - nature.com
In the past decade, membraneless assemblies known as biomolecular condensates have
been reported to play key roles in many cellular functions by compartmentalizing specific …

Selective autophagy receptor p62/SQSTM1, a pivotal player in stress and aging

AV Kumar, J Mills, LR Lapierre - Frontiers in cell and developmental …, 2022 - frontiersin.org
Efficient proteostasis is crucial for somatic maintenance, and its decline during aging leads
to cellular dysfunction and disease. Selective autophagy is a form of autophagy mediated by …

Regulation of nucleo-cytosolic 26S proteasome translocation by aromatic amino acids via mTOR is essential for cell survival under stress

I Livneh, V Cohen-Kaplan, B Fabre, I Abramovitch… - Molecular cell, 2023 - cell.com
The proteasome is responsible for removal of ubiquitinated proteins. Although several
aspects of its regulation (eg, assembly, composition, and post-translational modifications) …

PhaSepDB in 2022: annotating phase separation-related proteins with droplet states, co-phase separation partners and other experimental information

C Hou, X Wang, H Xie, T Chen, P Zhu… - Nucleic Acids …, 2023 - academic.oup.com
Phase separation (PS) proteins form droplets to regulate myriad membraneless organelles
(MLOs) and cellular pathways such as transcription, signaling transduction and protein …

Multiomic prediction of therapeutic targets for human diseases associated with protein phase separation

CM Lim, A González Díaz, M Fuxreiter… - Proceedings of the …, 2023 - National Acad Sciences
The phenomenon of protein phase separation (PPS) underlies a wide range of cellular
functions. Correspondingly, the dysregulation of the PPS process has been associated with …

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 …

Orphan quality control shapes network dynamics and gene expression

KG Mark, SDD Kolla, JD Aguirre, DM Garshott… - Cell, 2023 - cell.com
All eukaryotes require intricate protein networks to translate developmental signals into
accurate cell fate decisions. Mutations that disturb interactions between network …

Intracellular localization of the proteasome in response to stress conditions

C Enenkel, RW Kang, F Wilfling, OP Ernst - Journal of Biological Chemistry, 2022 - ASBMB
The ubiquitin–proteasome system fulfills an essential role in regulating protein homeostasis
by spatially and temporally controlling proteolysis in an ATP-and ubiquitin-dependent …

Loss of PML nuclear bodies in familial amyotrophic lateral sclerosis-frontotemporal dementia

F Antoniani, M Cimino, L Mediani, J Vinet… - Cell death …, 2023 - nature.com
Abstract Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two
neurodegenerative disorders that share genetic causes and pathogenic mechanisms. The …

Mechanistic insights into enhancement or inhibition of phase separation by different polyubiquitin chains

TP Dao, Y Yang, MF Presti, MS Cosgrove… - EMBO …, 2022 - embopress.org
Ubiquitin‐binding shuttle UBQLN2 mediates crosstalk between proteasomal degradation
and autophagy, likely via interactions with K48‐and K63‐linked polyubiquitin chains …