Publications related to Phosphorylation

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

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, Xiaoxu Li, Maroun Bou Sleiman, Jun Yong Kim

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

Genomics of Preaxostyla Flagellates Illuminates the Path Towards the Loss of Mitochondria

Marek Elias, Shweta Vinodrai Pipaliya

The notion that mitochondria cannot be lost was shattered with the report of an oxymonad Monocercomonoides exilis, the first eukaryote arguably without any mitochondrion. Yet, questions remain about whether this extends beyond the single species and how th ...

Public Library Science2023

Countering T cell exhaustion and senescence for enhanced adoptive T cell therapies against solid tumors

Yang Zhao

CAR-T cell therapy has shown remarkable success in treating hematopoietic malignancies, but its efficacy in solid tumors is limited by T cell dysfunction, including exhaustion and senescence. In this study, we designed metabolically armored CAR-T cells to ...

EPFL2023

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

Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation

Andrea Ablasser

Solid cancers exhibit a dynamic balance between cell death and proliferation ensuring continuous tumour maintenance and growth(1,2). Increasing evidence links enhanced cancer cell apoptosis to paracrine activation of cells in the tumour microenvironment in ...

NATURE PORTFOLIO2022

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

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

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

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

Johan Auwerx, Hilal Lashuel, Laurent Mouchiroud, Anass Chiki, Lara Petricca, 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

Mitochondrial copper depletion suppresses triple-negative breast cancer in mice

Elena Goun, Arkadiy Bazhin, Min Chen, Ji Qi

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

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

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

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

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, Nadine Aït Bouziad, Anass Chiki, 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

The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport

The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated t ...

2020

Niacin: an old lipid drug in a new NAD(+) dress

Johan Auwerx, Mario Romani, Elena Katsyuba, Dina Hofer

Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardi ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2019