A5024803085- RNA Research and Splicing
- Protein Kinase Regulation and GTPase Signaling
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Pancreatic function and diabetes
- ATP Synthase and ATPases Research
- Metabolism, Diabetes, and Cancer
- Genomics and Chromatin Dynamics
- Nuclear Structure and Function
- FOXO transcription factor regulation
- Cancer-related Molecular Pathways
- Enzyme Structure and Function
- Cancer-related gene regulation
- Fungal and yeast genetics research
- Endoplasmic Reticulum Stress and Disease
- HIV Research and Treatment
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Alkaline Phosphatase Research Studies
- Protein Structure and Dynamics
- Cellular transport and secretion
KU Leuven
2011-2020
VIB-KU Leuven Center for Cancer Biology
2015
University Medical Center Freiburg
2013
Universidad de Navarra
2013
Brown University
2012
University of California, San Diego
2011
Miyagi Prefectural Hospital Organization
2010
University of Oregon
2010
Scripps Research Institute
2010
Child Trends
2010
The ubiquitous protein Ser/Thr phosphatase-1 (PP1) interacts with dozens of regulatory proteins that are structurally unrelated. However, most them share a short, degenerate "RVxF"-type docking motif. Using broad in silico screening based on stringent definition the RVxF motif, combination multistep biochemical validation procedure, we have identified 78 novel mammalian PP1 interactors. A global analysis validated RVxF-based interactome not only provided insights into conserved features...
Most interactors of protein phosphatase-1 (PP1) contain a variant so-called "RVXF" sequence that binds to hydrophobic groove the catalytic subunit. A combination alignments and site-directed mutagenesis has enabled us further define consensus for this degenerate motif as [RK]-X0–1-[VI]-{P}-[FW], where X denotes any residue {P} except Pro. Naturally occurring RVXF sequences differ in their affinity PP1, we show by swapping experiments binding is an important determinant inhibitory potency...
Chromatin remodeling through histone posttranslational modifications (PTMs) and DNA methylation has recently been implicated in cognitive functions, but the mechanisms involved such epigenetic regulation remain poorly understood. Here, we show that protein phosphatase 1 (PP1) is a critical regulator of chromatin mammalian brain controls PTMs gene transcription associated with long-term memory. Our data PP1 present at cells interacts enzymes machinery including HDAC1 (histone deacetylase 1)...
Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM essential to achieve cure. The transcription factor FOXM1 has recently gained attention as master regulator mitotic progression cancer various organs. Here, we demonstrate forms protein complex with the kinase MELK GSCs, leading phosphorylation and activation kinase-dependent manner. This MELK-dependent results subsequent increase regulatory...
Recombinant muscle GYS1 (glycogen synthase 1) and recombinant liver GYS2 were phosphorylated by AMPK (AMP-activated protein kinase) in a time-dependent manner to similar stoichiometry. The phosphorylation site was identified as Ser7, which lies favourable consensus for AMPK. Phosphorylation of or led enzyme inactivation decreasing the affinity both UDP-Glc (UDP-glucose) [assayed absence Glc-6-P (glucose-6-phosphate)] (assayed at low concentrations). Incubation freshly isolated rat...
Abstract Maternal embryonic leucine zipper kinase (MELK) is a highly conserved serine/threonine initially found to be expressed in wide range of early cellular stages, and as result has been implicated embryogenesis cell cycle control. Recent evidence identified broader spectrum tissue expression pattern for this than previously appreciated. MELK several human cancers stem populations. Unique spatial temporal patterns within these tissues suggest that plays prominent role control,...
When glucose is added to cells of the yeast Saccharomyces cerevisiae grown on non-fermentable carbon sources, a cAMP signal induced which triggers protein phosphorylation cascade. Addition or fructose phosphoglucose isomerase mutant also indicating that metabolization sugar beyond phosphate step not necessary. Glucose 6-phosphate might stimulate triggering reaction since induction with shows significant delay. Experiments double and triple mutants in hexokinase 1, 2 glucokinase indicated...
Nuclei from bovine thymus contain a high level of partially latent protein phosphatase 1 (PP-1). More than 90% this PP-1 is associated with the insoluble chromatin/matrix fraction and can be extracted 0.3 M NaCl. The salt extract also contains three heat- acid-stable inhibitory proteins that resolved on Mono Q. We have purified two these nuclear inhibitors (NIPP-1a NIPP-1b) until homogeneity. They are acidic (pI = 4.4) molecular mass 18 kDa (NIPP-1a) 16 (NIPP-1b) SDS-PAGE. Judged larger was...
Addition of glucose to Saccharomyces cerevisiae cells grown on a nonfermentable carbon source triggers cyclic AMP (cAMP) signal, which induces protein phosphorylation cascade. In yeast strain lacking functional RAS1 and RAS2 genes containing bcy mutation suppress the lethality RAS deficiency, cAMP signal was absent. dinitrophenol, stimulates in vivo synthesis by lowering intracellular pH, also did not enhance level. A control strain, with present, showed responses similar those wild-type...
Addition of glucose to acetate-grown cells Saccharomyces cerevisiae caused a rapid transient increase in the cAMP level followed by 10-fold, activity trehalase. Ethidium bromide and acridine analogues inhibited both glucose-induced responses similar way, confirming role signal as second messenger sugar-induced activation When nitrogen sources or protein synthesis inhibitors were added after trehalase activity, reactivation occurred. In this case, however, there was only very small level,...
A cluster of phosphorylation sites in LRRK2 (leucine-rich repeat kinase 2), including Ser910, Ser935, Ser955 and Ser973, is important for PD (Parkinson's disease) pathogenesis as several PD-linked mutants are dephosphorylated at these sites. also cells after pharmacological inhibition its activity, which currently proposed a strategy disease-modifying therapy. Despite this importance dephosphorylation mutant pathological mechanism(s) LRRK2's response to inhibition, the mechanism by occurs...
The first cell-penetrating peptide that activates protein phosphatase-1 (PP1) by disrupting a subset of PP1 complexes in living cells has been developed. Activated rapidly dephosphorylates its substrates, counteracting kinase activity inside cells. Activation can thus be novel approach to study function and counteract Ser/Thr under pathologically increased signaling. phosphorylation proteins is fundamental signal transduction processes Malfunction these contributes the development progress...
Abstract RepoMan is a scaffold for signalling by mitotic phosphatases at the chromosomes. During (pro)metaphase, RepoMan-associated protein PP1 and PP2A-B56 regulate chromosome targeting of Aurora-B kinase RepoMan, respectively. Here we show that this task division critically dependent on phosphorylation Cyclin-dependent 1 (Cdk1), which reduces binding but facilitates recruitment PP2A-B56. The inactivation Cdk1 in early anaphase reverses phosphatase switch, resulting accumulation PP1-RepoMan...
Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein kinase, has oncogenic properties and is overexpressed in many cancer cells. The function of MELK attributed to its capacity disable critical cell-cycle checkpoints reduce replication stress. Most functional studies have relied on the use siRNA/shRNA-mediated gene silencing. In present study, we explored biological using MELK-T1, novel selective small-molecule inhibitor. Strikingly, MELK-T1 triggered rapid...