A5033984797- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- RNA modifications and cancer
- Skin and Cellular Biology Research
- Biochemical and Molecular Research
- Epigenetics and DNA Methylation
- Hair Growth and Disorders
- DNA Repair Mechanisms
- Lipid metabolism and biosynthesis
- Retinoids in leukemia and cellular processes
- Immunotherapy and Immune Responses
- Pediatric Hepatobiliary Diseases and Treatments
- Spondyloarthritis Studies and Treatments
- Alkaline Phosphatase Research Studies
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Pregnancy and Medication Impact
- Histone Deacetylase Inhibitors Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Telomeres, Telomerase, and Senescence
- Cellular transport and secretion
KU Leuven
2015-2025
VIB-KU Leuven Center for Brain & Disease Research
2021-2022
VIB-KU Leuven Center for Cancer Biology
2016
Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, more rarely PPP2R1A. Here, we aimed to better understand the latter characterizing 30 individuals often recurrent this PP2A scaffolding Aα subunit.Most cases were identified through routine clinical diagnostics. Variants biochemically characterized for activity interaction other subunits.We describe 16 different PPP2R1A, 21 of whom...
Protein phosphatase-1 (PP1) is a key regulator of transcription and targeted to promoter regions via associated proteins. However, the chromatin binding sites PP1 have never been studied in systematic genome-wide manner. Methylation-based DamID profiling HeLa cells has enabled us map hundreds three its major nuclear interactors, i.e. RepoMan, NIPP1 PNUTS. Our data reveal that α, β γ isoforms largely bind distinct subsets promoters can also be differentiated by their pattern. PP1β emerged as...
Abstract NIPP1 is one of the major nuclear interactors protein phosphatase PP1. The deletion in mice early embryonic lethal, which has precluded functional studies adult tissues. Hence, we have generated an inducible knockout model using a tamoxifen-inducible Cre recombinase transgene. inactivation encoding alleles ( Ppp1r8 ) occurred very efficiently testis and resulted gradual loss germ cells, culminating Sertoli-cell only phenotype. Before overt development this phenotype −/− showed...
Germ cell proliferation is epigenetically controlled, mainly through DNA methylation and histone modifications. However, the pivotal epigenetic regulators of germ self-renewal differentiation in postnatal testis are still poorly defined. The methyltransferase enhancer zeste homolog 2 (EZH2) catalytic subunit Polycomb repressive complex 2, represses target genes trimethylation H3 at Lys-27 (H3K27me3), interacts (in)directly with both protein phosphatase 1 (PP1) nuclear inhibitor PP1 (NIPP1)....
Abstract The Ppp1r8 gene encodes NIPP1, a nuclear interactor of protein phosphatase PP1. deletion NIPP1 is embryonic lethal at the gastrulation stage, which has hampered its functional characterization in adult tissues. Here, we describe effects conditional mouse liver epithelial cells. Ppp1r8−/− livers developed ductular reaction, that is, bile-duct hyperplasia with associated fibrosis. increased proliferation biliary cells was least partially due to an expansion progenitor cell compartment...
Liprin-α1 is a widely expressed scaffolding protein responsible for regulating cellular processes such as focal adhesion, cell motility, and synaptic transmission. interacts with many proteins including ELKS, GIT1, liprin-β, LAR-family receptor tyrosine phosphatase. Through these protein-protein interactions, liprin-α1 assembles large higher-order molecular complexes; however, the regulation of this complex assembly/disassembly unknown. Liquid-liquid phase separation (LLPS) process that...
Abstract Nuclear Inhibitor of PP1 (NIPP1) is a conserved regulatory subunit protein phosphatase PP1. The selective deletion NIPP1 in mouse liver parenchymal cells or skin epidermal culminates late-onset hyperproliferation subset resident progenitor cells. Although hyperplastic phenotype usually tumor promoting, we show here that the absence conferred strong resistance to chemically induced hepatocellular carcinoma. ablation did not affect metabolism administered mutagens (diethylnitrosamine...
Primary liver cancer (PLC) can be classified in hepatocellular (HCC), cholangiocarcinoma (CCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). The molecular mechanisms involved PLC development phenotype decision are still not well understood. Complete deletion of Ppp2r5d, encoding the B56δ subunit Protein Phosphatase 2A (PP2A), results spontaneous HCC mice via a c-MYC-dependent mechanism. In present study, we aimed to examine role Ppp2r5d an independent mouse model...
NIPP1 is a ubiquitously expressed regulatory subunit of PP1. Its embryonic deletion in keratinocytes causes chronic sterile skin inflammation, epidermal hyperproliferation, and resistance to mutagens adult mice. To explore the primary effects deletion, we first examined hair cycle progression knockouts (SKOs). The entry SKOs was delayed owing prolonged quiescence follicle stem cells. In contrast, second advanced as result precocious activation epidermis progressively accumulated senescent...
Psoriatic arthritis (PsA) is a complex, progressive, and often debilitating disease. Despite recent advances in treatment, numerous unmet needs patient care persist. Rheumacensus multistakeholder, pan-European initiative designed to identify ways elevate the standard of (SoC) treatment ambition for patients with PsA, using perspectives three key stakeholder groups: patients, healthcare professionals (HCPs) payors. followed phases: an insights-gathering workshop current PsA area focus...
PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by heterozygous alteration in one several genes encoding subunit type 2A protein phosphatases. Reported affected genes, so far, PPP2R5D , the PP2A regulatory B56δ subunit; PPP2R1A scaffolding Aα and PPP2CA catalytic Cα subunit—in that order frequency. Patients with pathogenic de novo mutation these part, present overlapping features, such as generalized hypotonia, intellectual delay, facial dysmorphologies,...