A5069985020- Endoplasmic Reticulum Stress and Disease
- Enzyme Structure and Function
- RNA Research and Splicing
- Protein Tyrosine Phosphatases
- Alkaline Phosphatase Research Studies
- RNA regulation and disease
- bioluminescence and chemiluminescence research
- Computational Drug Discovery Methods
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Protein Structure and Dynamics
- Trace Elements in Health
- Nicotinic Acetylcholine Receptors Study
- Ubiquitin and proteasome pathways
- Hereditary Neurological Disorders
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Toxin Mechanisms and Immunotoxins
- Mass Spectrometry Techniques and Applications
- PI3K/AKT/mTOR signaling in cancer
- Lipid Membrane Structure and Behavior
- Drug Transport and Resistance Mechanisms
- DNA Repair Mechanisms
- Biotin and Related Studies
KU Leuven
2014-2024
The integrated stress response (ISR) is regulated by kinases that phosphorylate the α subunit of translation initiation factor 2 and phosphatases dephosphorylate it. Genetic biochemical observations indicate eIF2αP-directed holophosphatase, a therapeutic target in diseases protein misfolding, comprised regulatory subunit, PPP1R15, catalytic phosphatase 1 (PP1). In mammals, there are two isoforms PPP1R15A PPP1R15B, with overlapping roles essential function eIF2αP dephosphorylation. However,...
SDS22 forms an inactive complex with nascent protein phosphatase PP1 and Inhibitor-3. SDS22:PP1:Inhibitor-3 is a substrate for the ATPase p97/VCP, which liberates binding to canonical regulatory subunits. The exact role of in PP1-holoenzyme assembly remains elusive. Here, we show that stabilizes PP1. In absence SDS22, gradually lost, resulting hyperphosphorylation proliferation arrest. Similarly, identify female individual severe neurodevelopmental disorder bearing unstable mutant,...
An emerging strategy for the therapeutic targeting of protein phosphatases involves use compounds that interfere with binding regulatory subunits or substrates. However, high-throughput screening strategies such interfering molecules are scarce. Here, we report on conversion NanoBiT split-luciferase system into a robust assay quantification phosphatase subunit and substrate interactions in cell lysates. The is suitable to screen small-molecule libraries compounds. We designed validated...
Protein phosphatase‐1 (PP1) complexed to nuclear inhibitor of PP1 (NIPP1) limits DNA repair through dephosphorylation NIPP1‐recruited substrates. However, the PP1:NIPP1 holoenzyme is completely inactive under basal conditions, hinting at a damage‐regulated activation mechanism. Here, we report that damage caused after time delay several hours phosphorylation NIPP1 C‐terminal tyrosine 335 (Y335) by Src‐family kinase. partially resulted from dissociation C terminus active site PP1. In...
The aminoguanidine compound robenidine is widely used as an antibiotic for the control of coccidiosis, a protozoal infection in poultry and rabbits. Interestingly, structurally similar to guanabenz (analogs), which are currently undergoing clinical trials cytoprotective agents management neurodegenerative diseases. Here we show that protect cells from tunicamycin-induced unfolded protein response degree. Both compounds also reduced tumor necrosis factor α-induced activation NF-κB. effects...
Protein phosphatase PP1 has two active‐site metals (Zn 2+ /Fe ) that are essential for catalysis. However, when expressed in bacteria, Mn ‐ions its active site, indicating the incorporation of Zn depends on additional eukaryotic component(s). Here, we used purified, metal‐deficient to study metal incorporation. Fe was incorporated spontaneously, but not. ‐incorporation at physiological pH depended co‐expression with PPP1R2 (Inhibitor‐2) or PPP1R11 (Inhibitor‐3), a pre‐incubation 4. We also...
Protein Ser/Thr phosphatase PP1 is always associated with one or two regulatory subunits RIPPOs. One of the earliest evolved RIPPOs PPP1R2, also known as Inhibitor-2. Since its discovery nearly 5 decades ago, PPP1R2 has been variously described an inhibitor, activator (metal) chaperone PP1, but it still unknown how affects function in intact cells. Here, using specific research tools, we demonstrate that stabilises a subgroup holoenzymes, exemplified by PP1:RepoMan, thereby promoting...
ABSTRACT The integrated stress response (ISR) is regulated by kinases that phosphorylate the α subunit of translation initiation factor 2 and phosphatases dephosphorylate it. Genetic biochemical observations indicate eIF2α P -directed holophosphatase - a therapeutic target in diseases protein misfolding comprised regulatory, PPP1R15, catalytic, Protein Phosphatase 1 (PP1) subunit. In mammals, there are two isoforms regulatory subunit, PPP1R15A PPP1R15B, with overlapping roles promoting...