A5088037590- Ubiquitin and proteasome pathways
- Toxin Mechanisms and Immunotoxins
- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Streptococcal Infections and Treatments
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Health, Environment, Cognitive Aging
- Nutrition, Genetics, and Disease
- Heat shock proteins research
- Calcium signaling and nucleotide metabolism
- Cancer, Hypoxia, and Metabolism
- Neutropenia and Cancer Infections
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Protease and Inhibitor Mechanisms
- Sirtuins and Resveratrol in Medicine
- Endoplasmic Reticulum Stress and Disease
- Blood disorders and treatments
- Toxoplasma gondii Research Studies
- Autophagy in Disease and Therapy
- Nuclear Structure and Function
- Genetics and Neurodevelopmental Disorders
Max Planck Institute for Biology of Ageing
2015-2023
University of Cologne
2022
Université de Montpellier
2019
Centre National de la Recherche Scientifique
2019
University of Dundee
2012-2019
Wellcome Trust
2012-2019
Cell and Gene Therapy Catapult
2012
Centre de Recherche en Biologie cellulaire de Montpellier
2012
Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that synthesise ADP-ribosylation (ADPr), reversible modification proteins regulates many different cellular processes. Several mammalian PARPs known to regulate the DNA damage response, but it is not clear which amino acids in primary ADPr targets. Previously, we reported ARH3 reverses newly discovered type (ADPr on serine residues; Ser-ADPr) and developed tools analyse this (Fontana et al., 2017). Here, show Ser-ADPr represents...
ADP-ribosylation is a post-translational modification (PTM) of proteins found in organisms from all kingdoms life which regulates many important biological functions including DNA repair, chromatin structure, unfolded protein response and apoptosis. Several cellular enzymes, such as macrodomain containing PARG [poly(ADP-ribose) glycohydrolase] TARG1 [terminal ADP-ribose (ADPr) glycohydrolase], reverse ADP-ribosylation. In the present study, we show that human Nudix (nucleoside...
Modification of proteins with ubiquitin and ubiquitin-like molecules is involved in the regulation almost every biological process. Historically, each conjugation pathway has its unique set E1, E2 E3 enzymes that lead to activation their cognate molecules. Here, we present unexpected finding under stress conditions, E1 enzyme Ube1 mediates molecule NEDD8. Inhibition 26S proteasome, heat shock oxidative cause a global increase NEDDylation. Surprisingly, this does not depend on NEDD8...
Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation fundamental cellular processes including metabolic homeostasis and genome integrity. We show existence a hitherto unrecognized class sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. our model organisms, Staphylococcus aureus Streptococcus pyogenes, activity is dependent on prior lipoylation...
Ubiquitin and ubiquitin-like chains are finely balanced by conjugating de-conjugating enzymes. Alterations in this balance trigger the response to stress conditions often observed pathologies. How such changes detected is not well understood. We identify HSP70 chaperone as a sensor of between mono- poly-NEDDylation. Upon DNA damage, induction de-NEDDylating enzyme NEDP1 restricts formation NEDD8 chains, mainly through lysines K11/K48. This promotes APAF1 oligomerization apoptosis induction,...
Abstract The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. SUMO-targeted ubiquitin ligase RNF4 engages with SUMO on linked substrates catalyses their ubiquitination, which targets for proteasomal degradation. Here we use a segmental labelling approach combined solution nuclear magnetic resonance (NMR) spectroscopy biochemical characterization to reveal how manipulates...
Abstract Histones modulate gene expression by chromatin compaction, regulating numerous processes such as differentiation. However, the mechanisms underlying histone degradation remain elusive. Human embryonic stem cells (hESCs) have a unique architecture characterized low levels of trimethylated H3 at lysine 9 (H3K9me3), heterochromatin-associated modification. Here we assess link between intrinsic epigenetic landscape and ubiquitin-proteasome system hESCs. We find that hESCs exhibit high...
Abstract Background The majority of BRCA1 -mutant breast cancers are characterized by a triple-negative phenotype and basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options limited, highlighting the need for development novel targeted therapies this tumor subtype. Methods Our group previously showed that EZH2 is functionally relevant in BRCA1-deficient tumors blocking enzymatic activity could be potent strategy. To validate role as therapeutic...
Regulation by the small modifier SUMO is heavily dependent on spatial control of enzymes that mediate attachment and removal substrate proteins. Here, we show in fission yeast Schizosaccharomyces pombe, delocalisation protease Ulp1 from nuclear envelope results centromeric defects can be attributed to hyper-SUMOylation at periphery. Unexpectedly, find although this localised impairs silencing, it also enhance centromere clustering. Moreover, both effects are least partially SUMOylation inner...
Abstract Regulation by the small modifier SUMO is heavily dependent on spatial control of enzymes that mediate attachment and removal substrate proteins. Here we show in fission yeast, delocalisation protease Ulp1 from nuclear envelope results centromeric defects can be attributed to hyper-SUMOylation at periphery. Unexpectedly, find while this localised impairs silencing, it also enhance centromere clustering. Moreover, both effects are least partially SUMOylation inner membrane protein...
Summary Ubiquitin and ubiquitin-like chains are finely balanced by the action of conjugating de-conjugating enzymes. Alterations in this balance trigger signalling events required for response to stress conditions often observed pathologies. How such changes detected is not well-understood. We show that upon DNA damage induction de-NEDDylating enzyme NEDP1 restricts formation poly-NEDD8 chains, mainly through lysines K11/K48. This promotes APAF1 oligomerisation apoptosis induction, a step...
Background The majority of BRCA1-mutant breast cancers are characterized by a triple-negative phenotype and basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options limited, highlighting the need for development novel targeted therapies this tumor subtype.