Regulation of proteasome assembly and activity in health and disease

A Rousseau, A Bertolotti - Nature reviews Molecular cell biology, 2018 - nature.com
The proteasome degrades most cellular proteins in a controlled and tightly regulated
manner and thereby controls many processes, including cell cycle, transcription, signalling …

CRISPRi and CRISPRa screens in mammalian cells for precision biology and medicine

M Kampmann - ACS chemical biology, 2018 - ACS Publications
Next-generation DNA sequencing technologies have led to a massive accumulation of
genomic and transcriptomic data from patients and healthy individuals. The major challenge …

Mitochondrial metabolism promotes adaptation to proteotoxic stress

P Tsvetkov, A Detappe, K Cai, HR Keys… - Nature chemical …, 2019 - nature.com
The mechanisms by which cells adapt to proteotoxic stress are largely unknown, but are key
to understanding how tumor cells, particularly in vivo, are largely resistant to proteasome …

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens

DW Morgens, M Wainberg, EA Boyle, O Ursu… - Nature …, 2017 - nature.com
CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome
function, but can be confounded by nuclease-induced toxicity at both on-and off-target sites …

Systematic comparison of CRISPR/Cas9 and RNAi screens for essential genes

DW Morgens, RM Deans, A Li, MC Bassik - Nature biotechnology, 2016 - nature.com
We compared the ability of short hairpin RNA (shRNA) and CRISPR/Cas9 screens to identify
essential genes in the human chronic myelogenous leukemia cell line K562. We found that …

Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1

NJ Lehrbach, G Ruvkun - elife, 2016 - elifesciences.org
Proteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular
function, transcription of proteasome subunit genes is induced in response to proteasome …

The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation

K Bhattacharya, L Weidenauer, TM Luengo… - Nature …, 2020 - nature.com
Abstract Hop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate
transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key …

Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness

BW Tye, N Commins, LV Ryazanova, M Wühr… - elife, 2019 - elifesciences.org
To achieve maximal growth, cells must manage a massive economy of ribosomal proteins (r-
proteins) and RNAs (rRNAs) to produce thousands of ribosomes every minute. Although …

Alternative systems for misfolded protein clearance: life beyond the proteasome

HE Johnston, RS Samant - The FEBS journal, 2021 - Wiley Online Library
Protein misfolding is a major driver of ageing‐associated frailty and disease pathology.
Although all cells possess multiple, well‐characterised protein quality control systems to …

Golgi organization is regulated by proteasomal degradation

A Eisenberg-Lerner, R Benyair, N Hizkiahou… - Nature …, 2020 - nature.com
The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis.
Perturbations in Golgi structure are associated with numerous disorders from …