Publications associées à Mutant Exon1 Huntingtin Aggregation is Regulated by T3 Phosphorylation-Induced Structural Changes and Crosstalk between T3 Phosphorylation and Acetylation at K6

Investigating the intra-molecular and inter-molecular effects of post-translational modifications on intrinsically disordered protein regions and structured protein regions

Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...

EPFL2024

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

Rational combination platform trial design for children and young adults with Diffuse Midline Glioma: a report from PNOC

Sebastian Martin Waszak

Diffuse midline glioma (DMG) is a devastating pediatric brain tumor unresponsive to hundreds of clinical trials. Approximately 80% of DMGs harbor H3K27M oncohistones, which reprogram the epigenome to increase the metabolic profile of the tumor cells. We ha ...

2023

Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice

Johan Auwerx, Maroun Bou Sleiman, Jun Yong Kim, Xiaoxu Li

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Here, Park et al. identify LETMD1 as a mitochondrial matrix protein enriched in brown adipose tissue (BAT) and reveal a crucial ro ...

Nature Portfolio2023

SLC25A46 promotes mitochondrial fission and mediates resistance to lipotoxic stress in INS-1E insulin-secreting cells

Loïc Dayon, Andreas Wiederkehr

Glucose sensing in pancreatic D-cells depends on oxidative phosphorylation and mitochondria-derived signals that promote insulin secretion. Using mass spectrometry-based phosphoproteo-mics to search for downstream effectors of glucose-dependent signal tran ...

COMPANY BIOLOGISTS LTD2023

Role of the cystathionine beta-synthase / H2S pathway in the development of cellular metabolic dysfunction and pseudohypoxia in down syndrome

Theodora Panagaki

Background: Overexpression of the transsulfuration enzyme cystathionine-beta-synthase (CBS), and overproduction of its product, hydrogen sulfide (H2S) are recognized as potential pathogenetic factors in Down syndrome (DS). The purpose of the study was to d ...

ELSEVIER2022

Regulation of Src tumor activity by its N-terminal intrinsically disordered region

Florence Armand, Romain Hamelin

The membrane-anchored Src tyrosine kinase is involved in numerous pathways and its deregulation is involved in human cancer. Our knowledge on Src regulation relies on crystallography, which revealed intramolecular interactions to control active Src conform ...

SPRINGERNATURE2022

Epigenetic plasticity as a signature for memory allocation

Giulia Santoni

Long-lasting memories are stored in a small set of neurons scattered throughout the brain, so-called engram cells. To define a stable engram each region of the brain involved in memory storage recruits between 5 and 20 percent of excitatory neurons. In par ...

EPFL2022

Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function

Matteo Dal Peraro, Maria Josefina Marcaida Lopez

Deficiency of the serine hydrolase prolyl endopeptidase-like (PREPL) causes a recessive metabolic disorder characterized by neonatal hypotonia, feeding difficulties, and growth hormone deficiency. The pathophysiology of PREPL deficiency and the physiologic ...

CELL PRESS2021

Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation

Hilal Lashuel, Anass Chiki, Matteo Dal Peraro, Luciano Andres Abriata, Lucien Fabrice Krapp, Driss Boudeffa, Rajasekhar Kolla, Zhidian Zhang, Iman Rostami

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of the Huntingtin protein (Htt) have been shown to inhibit the aggregation and attenuate the toxicity of mutant Htt proteins in vitro and in various models of Huntington’s disea ...

2021

Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation

Ludovica Vanzan

Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated geno ...

OXFORD UNIV PRESS2021

The Nt17 Domain and its Helical Conformation Regulate the Aggregation, Cellular Properties and Neurotoxicity of Mutant Huntingtin Exon 1

Giovanni Dietler, Hilal Lashuel, Anass Chiki, Francesco Simone Ruggeri, Anne-Laure Mahul Mellier, Sophie Vieweg, Sean Michael Deguire, Urszula Beata Cendrowska, Nathan Alain Denis Riguet

Converging evidence points to the N-terminal domain comprising the first 17 amino acids of the Huntingtin protein (Nt17) as a key regulator of its aggregation, cellular properties and toxicity. In this study, we further investigated the interplay between N ...

Elsevier2021

Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases

Hilal Lashuel, Anass Chiki, Ramanath Narayana Hegde, Luciano Andres Abriata, Andreas Reif, Driss Boudeffa, Jonathan Jean-Pierre Ricci

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of exon 1 of the Huntingtin protein (Httex1) play important roles in modulating its cellular properties and functions in health and disease. In particular, phosphorylation of th ...

2020

Cellulose phosphorylation comparison and analysis of phosphorate position on cellulose fibers

David Lyndon Emsley, Jayasubba Reddy Yarava, Michel Bardet, Julien Bras

Chemical modifications of cellulose fibers as pretreatment for cellulose nanofibrils (CNF) production have been investigated to improve the production process and the quality of obtained cellulosic nanomaterial. In this study, phosphorylation of cellulose ...

ELSEVIER SCI LTD2020

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

Hilal Lashuel, Anass Chiki, Johan Auwerx, Ramanath Narayana Hegde, Laurent Mouchiroud, Lara Petricca

Phosphorylation of the N‐terminal domain of the huntingtin (HTT ) protein has emerged as an important regulator of its localization, structure, aggregation, clearance and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and ...

2020

Mitochondrial copper depletion suppresses triple-negative breast cancer in mice

Elena Goun, Arkadiy Bazhin, Ji Qi, Min Chen

Depletion of mitochondrial copper, which shifts metabolism from respiration to glycolysis and reduces energy production, is known to be effective against cancer types that depend on oxidative phosphorylation. However, existing copper chelators are too toxi ...

NATURE RESEARCH2021

Crosstalk between Drp1 phosphorylation sites during mitochondrial dynamics and metabolic adaptation

Miriam Valera Alberni

Mitochondria are highly dynamics organelles that undergo coordinated cycles of fission and fusion, referred to as mitochondrial dynamics. Mitochondrial dynamics regulate mitochondrial bioenergetics and allow cells to adapt to changing cellular stresses and ...

EPFL2020

Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau

Hilal Lashuel, Anass Chiki, Nadine Aït Bouziad, Galina Limorenko

The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau's norma ...

2020

Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents

Sonia Donzelli

The contraction and relaxation of the heart is controlled by stimulation of the beta 1-adrenoreceptor (AR) signaling cascade, which leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation. Phosphorylation i ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2020

Targeting the oncogenic signaling of the transcription factor STAT3 with potent and selective monobody inhibitors

Grégory La Sala

Many targeted cancer therapies fail to improve the overall survival of patients. Limitations involve low drug selectivity and the rapid development of resistance. Moreover, the majority of oncogenic drivers presently remain considered as undruggable as th ...

EPFL2020