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Concept

Protein phosphorylation

Related publications (33)

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

Zhidian Zhang

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

Discovery of macrocyclic inhibitors of challenging protein-protein interactions

Edward Jeffrey Will

Macrocycles are a therapeutic modality of interest for drugging challenging disease targets due to their high binding affinity and membrane permeability, enabling the discovery of orally delivered and efficacious therapeutics. Recent methods have enabled t ...

EPFL2024

Keap It in the Family: How to Fish out New Paradigms in Keap1-Mediated Cell Signaling

Yimon Aye, Kuan-Ting Huang

Keap1 is associated with cytoprotective signaling. These roles of Keap1 typically focus on its role as a degrader of the antioxidant response (AR) transcription factor, Nrf2, and the inhibition of this process upon Keap1 labeling by electrophiles. However, ...

Wiley-V C H Verlag Gmbh2023

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases

Hilal Lashuel, Johannes Burtscher, Melek Firat Altay, Somanath Jagannath

The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance amo ...

Nature Portfolio2023

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

Romain Hamelin, Florence Armand

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

Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

Melek Firat Altay

Synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy (MSA) are detrimental neurodegenerative diseases. Alpha-synuclein (aSyn), the main aggregating protein found in the pathological inclusions of these ailmen ...

EPFL2022

Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutS gamma complex

Alexander Woglar

Crossover formation is essential for proper segregation of homologous chromosomes during meiosis. Here, we show that Caenorhabditis elegans cyclin-dependent kinase 2 (CDK-2) partners with cyclin-like protein COSA-1 to promote crossover formation by promoti ...

National Academy of Sciences2022

Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson's Disease and Multiple System Atrophy

Hilal Lashuel, Melek Firat Altay

Aggregated alpha-synuclein (alpha-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA ...

MDPI2022

Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity

Hilal Lashuel, Nicolas Jean Philippe Guex, Anass Chiki, Christian Iseli, Anne-Laure Mahul Mellier, Ritwik Burai, Melek Firat Altay, Jonathan Jean-Pierre Ricci, Salvatore Novello, Pedro José Santana Ribeiro Magalhães, Sonia Donzelli, Yllza Jasiqi, Ramanath Narayana Hegde, Sean Michael Deguire, Ahmed Sherif Saad Zaghloul Mohamed Sadek

Antibodies against phosphorylated alpha-synuclein (aSyn) at 5129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson's disease and other neurodegenerative dis ...

NATURE PORTFOLIO2022

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration

Hilal Lashuel, Sonia Donzelli

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteost ...

2021

An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease

Christopher Clark

Background Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypot ...

2021

A New Chemoenzymatic Semisynthetic Approach Provides Insight into the Role of Phosphorylation beyond Exon1 of Huntingtin and Reveals N-Terminal Fragment Length-Dependent Distinct Mechanisms of Aggregation

Hilal Lashuel, Rajasekhar Kolla, Jonathan Jean-Pierre Ricci, Andreas Reif, Gopinath Pushparathinam

Huntington’s disease is a neurodegenerative dis- order caused by the expansion of a polyglutamine repeat (>36Q) in the N-terminal domain of the huntingtin protein (Htt), which renders the protein or fragments thereof more prone to aggregate and form inclus ...

2021

Porous silicon-A versatile platform for mass-production of ultrasensitive SERS-active substrates

Siarhei Zavatski

Surface-enhanced Raman scattering (SERS) spectroscopy is one of the most prospective methods combining state-of-the-art nanomaterials and optical techniques for highly sensitive express-analysis and detection of organic and bioorganic objects in liquids an ...

ELSEVIER2021

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, Urszula Beata Cendrowska, Sophie Vieweg, Nathan Alain Denis Riguet, Sean Michael Deguire

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

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

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

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

Site-Specific Hyperphosphorylation Inhibits, Rather than Promotes, Tau Fibrillization, Seeding Capacity, and Its Microtubule Binding

Hilal Lashuel, Rajasekhar Kolla, Mahmood Haj Yahya, Gopinath Pushparathinam

The consistent observation of phosphorylated tau in the pathology of Alzheimer's disease has contributed to the emergence of a model where hyperphosphorylation triggers both tau disassociation from microtubules and its subsequent aggregation. Herein, we ap ...

Wiley-VCH Verlag GmbH2020

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

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

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

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

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

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

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

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

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

Cellulose phosphorylation comparison and analysis of phosphorate position on cellulose fibers

David Lyndon Emsley, Jayasubba Reddy Yarava

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