A5007105384- PARP inhibition in cancer therapy
- Calcium signaling and nucleotide metabolism
- Toxin Mechanisms and Immunotoxins
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Mosquito-borne diseases and control
- Metabolism, Diabetes, and Cancer
- Diet, Metabolism, and Disease
- Cancer, Hypoxia, and Metabolism
- Cardiac Fibrosis and Remodeling
- Viral Infections and Outbreaks Research
- Cell Adhesion Molecules Research
- Cancer, Lipids, and Metabolism
- DNA Repair Mechanisms
- Cannabis and Cannabinoid Research
- Peptidase Inhibition and Analysis
- Herpesvirus Infections and Treatments
- CRISPR and Genetic Engineering
- Signaling Pathways in Disease
- Cancer-related gene regulation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
RWTH Aachen University
2017-2024
VIB-KU Leuven Center for Cancer Biology
2024
KU Leuven
2024
Abstract Human pathogenic positive single strand RNA ((+)ssRNA) viruses, including Chikungunya virus, pose severe health problems as for many neither efficient vaccines nor therapeutic strategies exist. To interfere with propagation, viral enzymatic activities are considered potential targets. Here we addressed the function of macrodomains, conserved folds non-structural proteins (+)ssRNA viruses. Macrodomains closely associated ADP-ribose and metabolism. ADP-ribosylation is a...
Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity ontogeny beyond to myofibroblast differentiation, newly identified populations remain ill defined, respect both molecular cues driving their differentiation subsequent role in fibrosis. Using an unbiased approach, we metalloprotease ADAMTS12 as a...
Replication of viruses requires interaction with host cell factors and repression innate immunity. Recent findings suggest that a subset intracellular mono-ADP-ribosylating PARPs, which are induced by type I interferons, possess antiviral activity. Moreover, certain RNA viruses, including Chikungunya virus (CHIKV), encode mono-ADP-ribosylhydrolases. Together, this suggests role for mono-ADP-ribosylation (MARylation) in host-virus conflicts, but the relevant substrates have not been...
Abstract The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status that crucial for adaptive response to limited availability. AMPK implicated in regulation many processes, including autophagy. However, precise mechanisms by which controls these processes and identities relevant substrates are not fully understood. Using microarrays, we identify Cyclin Y as an substrate phosphorylated at Serine 326 (S326) both vitro cells. Phosphorylation S326 promotes its...
Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple units to substrates, resulting mono- poly-ADP-ribosylation. TARG1/C6orf130 macrodomain that hydrolyzes mono-ADP-ribosylation interacts poly-ADP-ribose chains. Interactome analyses revealed TARG1 binds strongly ribosomes proteins rRNA processing ribosomal...
Abstract A subset of intracellular mono-ADP-ribosyltransferases diphtheria toxin-like (ARTDs, aka mono-PARPs) is induced by type I interferons. Some these mono-ARTDs feature antiviral activity while certain RNA viruses, including Chikungunya virus (CHIKV), encode mono-ADP-ribosylhydrolases, suggesting a role for mono-ADP-ribosylation (MARylation) in host-virus conflicts. CHIKV expresses four non-structural proteins (nsP1-nsP4), with nsP3 containing macrodomain that hydrolyzes and thereby...