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Concept

Proteasome

Related publications (31)

The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

Andrea Ablasser, Jonathan Jean-Pierre Ricci, Baptiste Claude André Guey, Chong Liu, Pengbiao Xu, Ying Liu, Lingyun Li, Pauline Ambre Melenec

Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2 ' 3 '-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA d ...

Nature Portfolio2024

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Pauline Franz

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

EPFL2024

Coordination of protein synthesis and degradation in mammalian cells

Shoujie Sun

The cellular protein levels are determined by protein synthesis and turnover rates. Two processes are involved in the proteome's turnover in proliferating cells: protein degradation and dilution. In theory, maintaining the cellular proteome concentration, ...

EPFL2023

An integrative approach to elucidate the mechanisms and dynamics of Huntingtin aggregation and inclusion formation in neuronal models of Huntington's Disease

Nathan Alain Denis Riguet

Despite the fact that the gene responsible for Huntington's disease (HD) is known, we still do not understand the underlying mechanisms leading to neurodegeneration and death. Identifying and understanding the mechanisms controlling mutant huntingtin (mHtt ...

EPFL2022

Gentle nano-electrospray ion source for reliable and efficient generation of microsolvated ions

Oleg Boyarkine, Vladimir Kopysov, Andrei Zviagin

We present herein the design of a nano-electrospray ion source capable of reliable generation of large quantities of microsolvated ions. The source is based on a triple molecular skimmer scheme and can be quickly tuned to generate bare ions or their ionic ...

AIP Publishing2022

A fluorescent multi-domain protein reveals the unfolding mechanism of Hsp70

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Salvatore Assenza, Satyam Tiwari

Detailed understanding of the mechanism by which Hsp70 chaperones protect cells against protein aggregation is hampered by the lack of a comprehensive characterization of the aggregates, which are typically heterogeneous. Here we designed a reporter chaper ...

Nature Research2023

TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin

Pierre Gönczy, Coralie Busso, Fernando Romero Balestra, Benita Wolf, Tessa Vivianne Averink

TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we chara ...

2021

Endoplasmic Reticulum and Lysosomal Quality Control of Four Nonsense Mutants of Iduronate 2-Sulfatase Linked to Hunter's Syndrome

Maurizio Molinari, Andrea Cavalli

Hunter's syndrome (mucopolysaccharidosis type II) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. Motivated by the case of a child affected by this syndrome, we compared the intracellular fate of w ...

2020

Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity

Hilal Lashuel, Anass Chiki

As an intrinsically disordered protein, monomeric alpha-synuclein (aSyn) occupies a large conformational space. Certain conformations lead to aggregation prone and non-aggregation prone intermediates, but identifying these within the dynamic ensemble of mo ...

Nature Research2020

Regulatory T cells engineered with TCR signaling-responsive IL-2 nanogels suppress alloimmunity in sites of antigen encounter

Li Tang, Na Li

Adoptive cell transfer of ex vivo expanded regulatory T cells (T-r(egs)) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such T-reg therapies to the clinic has been slow. Because T-reg homeostas ...

2020

Catechol Containing Polyelectrolyte Complex Nanoparticles as Local Drug Delivery System for Bortezomib at Bone Substitute Materials

Martin Guillermo Mueller, Jeremy Pak Hei Wong

The proteasome inhibitor bortezomib (BZM) is one of the most potent anti-cancer drugs in the therapy of multiple myeloma. In this study, an adhesive drug delivery system (DDS) for BZM was developed. Therefore, we extended the present DDS concept of polyele ...

2020

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

Oliver Hantschel, Florence Pojer, Kelvin Ka Ching Lau, Tim Kükenshöner, Grégory La Sala

The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere ...

Nature Research2020

Proteasomal and lysosomal clearance of faulty secretory proteins: ER-associated degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD) pathways

Maurizio Molinari

About 40% of the eukaryotic cell's proteins are inserted co- or post-translationally in the endoplasmic reticulum (ER), where they attain the native structure under the assistance of resident molecular chaperones and folding enzymes. Subsequently, these pr ...

2019

Schwann cells ER-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice

Maurizio Molinari

In the peripheral nervous system (PNS) myelinating Schwann cells synthesize large amounts of myelin protein zero (P0) glycoprotein, an abundant component of peripheral nerve myelin. In humans, mutations in P0 cause the demyelinating Charcot-Marie-Tooth 1B ...

2019

Targeted protein degradation through cytosolic delivery of monobody binders using bacterial toxins

Oliver Hantschel, Nadine Eliane Schmit, Katyayanee Neopane

Monobodies are small engineered binding proteins that, upon expression in cells, can inhibit signaling of cytosolic oncoproteins with outstanding selectivity. Efficacy may be further increased by inducing degradation of monobody targets through fusion to t ...

2019

Analysis of the S. pombe Meiotic Proteome Reveals a Switch from Anabolic to Catabolic Processes and Extensive Post-transcriptional Regulation

Viesturs Simanis, Marc Moniatte, Romain Hamelin, Florence Armand, Andrea Krapp, Lucien Fabrice Krapp, Diego Chiappe

Meiotic progression in S. pombe is regulated by stage-specific gene expression and translation, changes in RNA stability, expression of anti-sense transcripts, and targeted proteolysis of regulatory proteins. We have used SILAC labeling to examine the rela ...

2019

Proteomics and Beyond: Cell Decision-Making Shaped by Reactive Electrophiles

Yimon Aye, Xuyu Liu

Revolutionary proteomic strategies have enabled rapid profiling of the cellular targets of electrophilic small molecules. However, precise means to directly interrogate how these individual electrophilic modifications at low occupancy functionally reshape ...

2019

Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates

Felix Naef, David Michael Suter, Eric Paquet, Andrea Brigitta Alber

Cells need to reliably control their proteome composition to maintain homeostasis and regulate growth. How protein synthesis and degradation interplay to control protein expression levels remains unclear. Here, we combined a tandem fluorescent timer and pu ...

CELL PRESS2018

Chemical Ligand Space of Cereblon

Iuliia Boichenko

The protein cereblon serves as a substrate receptor of a ubiquitin ligase complex that can be tuned toward different target proteins by cereblon-binding agents. This approach to targeted protein degradation is exploited in different clinical settings and h ...

2018

Potential-induced nanoclustering of metallic catalysts during electrochemical CO2 reduction

Nicola Marzari, Raffaella Buonsanti, Emad Oveisi, Anna Loiudice, Oliviero Andreussi, Jianfeng Huang, Nicolas Georg Hörmann, Gian Luca De Gregorio

In catalysis science stability is as crucial as activity and selectivity. Understanding the degradation pathways occurring during operation and developing mitigation strategies will eventually improve catalyst design, thus facilitating the translation of b ...

Nature Research2018