Publications associées à Ubiquitine ligase

The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

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

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

Ion Spectroscopy Reveals Structural Difference for Proteins Microhydrated by Retention and Condensation of Water

Oleg Boyarkine, Andrei Zviagin

Protein ubiquitin in its +7 charge state microhydrated by 5 and 10 water molecules has been interrogated in the gas phase by cold ion UV/IR spectroscopy. The complexes were formed either by condensing water onto the unfolded bare proteins in a temperature- ...

Amer Chemical Soc2024

Autorepression of yeast Hsp70 cochaperones by intramolecular interactions involving their J-domains

Paolo De Los Rios, Satyam Tiwari, Pierre Goloubinoff, Bruno Claude Daniel Fauvet, Mathieu Rebeaud, Adélaïde Alice Mohr

The 70 kDa heat shock protein (Hsp70) chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) coevolved with Hsp70s to trigger ATP hydrolysis and catalytically upload various substrate polypeptides in ne ...

Elsevier Science Inc2024

Revealing chromatin-specific functions of histone deacylases

Beat Fierz, Carlos Moreno Yruela

Histone deacylases are erasers of Nε-acyl-lysine post-translational modifications and have been targeted for decades for the treatment of cancer, neurodegeneration and other disorders. Due to their relatively promiscuous activity on peptide substrates in v ...

2024

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

Bridging Native and Intrinsic Structures of Microhydrated Biomolecules by Cold Ion Spectroscopy

Andrei Zviagin

Solving native structures of such large molecules, like biomolecules, is often challenging, particularly due to the potentially infinite number of non-covalent interactions with water. In this thesis, we report the use of cold ion gas-phase action spectros ...

EPFL2023

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

Oleg Boyarkine, Andrei Zviagin, Vladimir Kopysov

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

Intrinsically High Capacity of Animal Cells From a Symbiotic Cnidarian to Deal With Pro-Oxidative Conditions

Gaëlle Delphine Toullec

The cnidarian-dinoflagellate symbiosis is a mutualistic intracellular association based on the photosynthetic activity of the endosymbiont. This relationship involves significant constraints and requires co-evolution processes, such as an extensive capacit ...

FRONTIERS MEDIA SA2022

Variants in USP48 encoding ubiquitin hydrolase are associated with autosomal dominant non-syndromic hereditary hearing loss

Nicolas Jean Philippe Guex

Non-Syndromic Hereditary Hearing Loss (NSHHL) is a genetically heterogeneous sensory disorder with about 120 genes already associated. Through exome sequencing (ES) and data aggregation, we identified a family with six affected individuals and one unrelate ...

Oxford University Press2021

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

Florence Pojer, Kelvin Ka Ching Lau, Oliver Hantschel, 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

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

Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells

Sebastian Martin Waszak, Ruxandra-Andreea Lambuta

TP53 deficiency is the most common alteration in cancer; however, this alone is typically insufficient to drive tumorigenesis. To identify genes promoting tumorigenesis in combination with TP53 deficiency, we perform genome-wide CRISPR-Cas9 knockout screen ...

2020

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

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

DNA repair protein Rad18 restricts LINE-1 mobility

Priscilla Turelli

Long interspersed element-1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome. L1 utilizes an endonuclease to insert L1 cDNA into the target genomic DNA, which induces double-strand DNA breaks in the human genome and activat ...

Nature Research2018

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

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

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

Cytosolic delivery and characterization of monobodies interfering with SH2 domain-phosphotyrosine interactions

Nadine Eliane Schmit

Targeted cancer therapy is a very promising concept; however, small molecule inhibitors only exist for a limited number of oncoproteins and resistance development limits their clinical use. Different engineered non-antibody scaffolds are being explored to ...

EPFL2018

Dynamic protein-chromatin interactions in heterochromatin and during the DNA damage response on the single molecule level

Andreas Linus Bachmann

Dynamic regulation of chromatin, a structure consisting of DNA and histone proteins, is mediated through histone post-translational modifications (PTMs) and effector proteins. HP1a and PRC2 are recruited to repressive PTMs (H3K9me3, H3K27me3) and enable he ...

EPFL2018

Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein by RAPTA complexes and its E3 ubiquitin ligase activity

Paul Joseph Dyson, Laure Menin, Luc Patiny

RAPTA compounds, ([Ru(eta(6)-arene)(PTA)Cl-2], PTA = 1,3,5-triaza-7-phosphaadamantane), have been reported to overcome drug resistance in cisplatin resistant cells. However, the exact mechanism of these complexes is still largely unexplored. In this study, ...

Elsevier2017