A5004685695- Dermatology and Skin Diseases
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- 14-3-3 protein interactions
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Advanced Proteomics Techniques and Applications
- Toxin Mechanisms and Immunotoxins
- RNA modifications and cancer
- Allergic Rhinitis and Sensitization
- PARP inhibition in cancer therapy
- IL-33, ST2, and ILC Pathways
- Advanced Biosensing Techniques and Applications
- RNA regulation and disease
- Protein purification and stability
- Cancer-related molecular mechanisms research
- Urticaria and Related Conditions
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Lipid metabolism and biosynthesis
- Protein Kinase Regulation and GTPase Signaling
- Genetic and Kidney Cyst Diseases
- Asthma and respiratory diseases
Leo Pharma (Denmark)
2019-2023
University of Copenhagen
2014-2021
Leiden University Medical Center
2019
Novo Nordisk Foundation
2014-2016
Universal proteomics sample preparation is challenging because of the high heterogeneity biological samples. Here we describe a novel mechanism that exploits inherent instability denatured proteins for nonspecific immobilization on microparticles by protein aggregation capture. To demonstrate general applicability this mechanism, analyzed phosphoproteomes, tissue proteomes, and interaction proteomes as well dilute secretomes. The findings present practical, sensitive cost-effective method....
DNA double-strand breaks (DSBs) at RNA polymerase II (RNAPII) transcribed genes lead to inhibition of transcription. The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in transcription DSBs by stimulating proteasome-dependent eviction RNAPII these lesions. How DNA-PK triggers inhibit remains unclear. Here we show that the HECT E3 ubiquitin ligase WWP2 associates with components and complexes is recruited genes. In response DSBs, targets subunit RPB1 for K48-linked...
Abstract Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in DNA that globally affect transcription and splicing. However, signaling pathways mechanisms link UV-light-induced damage to changes RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics protein kinase inhibition provide a systems view on phosphorylation patterns induced by UV uncover dependencies events canonical ATM/ATR p38 MAP pathway. We identify RNA-binding proteins...
Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 identified more than 40,000 phosphorylation sites, including many sites without additional enrichment. The analysis revealed RTK-specific regulation hundreds pTyr on key molecules. found the...
Inflammatory signaling is restricted through degradation and the translational repression of cytokine mRNAs. A key factor in this regulation tristetraprolin (TTP), an RNA-binding protein (RBP) that recruits RNA-destabilizing factors translation inhibitory complex 4EHP-GIGYF1/2 to AU-rich element (ARE)-containing Here, we show RBP ZNF598 contributes same regulatory module a TTP-like manner. Similar TTP, harbors three proline-rich motifs bind GYF domain GIGYF1. RNA sequencing experiments...
The interleukin (IL)-23/IL-17 immune axis is of central importance in psoriasis. However, the impact IL-17 family cytokines other than IL-17A psoriasis has not been fully established.To elucidate contribution psoriasis.To address expression and localization cytokines, lesional nonlesional skin samples from patients with were analysed by several complementary methods, including quantitative polymerase chain reaction, immunoassays, situ hybridization immunohistochemistry. Mechanistic studies...
Abstract Centriolar satellites (CS) are small granular structures that cluster in the vicinity of centrosomes. CS highly susceptible to stress stimuli, triggering abrupt displacement key factors. Here we discover a linear p38-MK2-14-3-3 signalling pathway specifically targets CEP131 trigger remodelling after cell stress. We identify as substrate p38 effector kinase MK2 and pinpoint S47 S78 critical phosphorylation sites CEP131. Ultraviolet-induced these residues generates direct binding for...
Abstract Tristetraprolin (TTP) is an RNA-binding protein and essential factor of posttranscriptional repression cytokine biosynthesis in macrophages. Its activity temporally inhibited by LPS-induced p38MAPK/MAPKAPK2/3–mediated phosphorylation, leading to a rapid increase expression. We compared TTP expression production mouse bone marrow–derived macrophages different genotypes: wild type, MAPKAP kinase 2 (MK2) deletion (MK2 knockout [KO]), MK2/3 double (MK2/3 KO [DKO]), TTP-S52A-S178A...
Tralokinumab, a fully human mAb specifically targeting the IL-13 cytokine, has demonstrated clinical efficacy and safety in patients with moderate-to-severe atopic dermatitis. Tralokinumab binds high affinity, which prevents interaction of IL-13Rα1 subsequent signaling. Similarly, tralokinumab-bound cannot bind to IL-13Rα2, proposed decoy receptor that is reported extraordinarily affinity. It however not been elucidated what extent tralokinumab interferes endogenous regulation through...
p38 and c-Jun N-terninal kinase (JNK) are activated in response to acute stress inflammatory signals. Through modification of a plethora substrates, these kinases profoundly re-shape cellular physiology for the optimal harmful environment and/or an state. Here, we utilized phospho-proteomics identify several hundred substrates both kinases. Our results indicate that scale signaling from JNK similar magnitude. Among many new targets, highlight regulation transcriptional regulators...
Centriolar satellites (CS) are small proteinaceous granules that cluster around the centrosome and serve as cargo vehicles for centrosomal proteins. It is generally accepted CS support a number of canonical specialized functions. Consequently, these highly dynamic structures target regulation by several cellular signalling pathways. Two decades research have led to identification large molecular components new biological roles CS. Here, we summarize latest advances in continuous efforts...
ABSTRACT Universal proteomics sample preparation is challenging due to the high heterogeneity of biological samples. Here we describe a novel mechanism that exploits inherent instability denatured proteins for non-specific immobilization on microparticles by protein aggregation capture. To demonstrate general applicability this mechanism, analyzed phosphoproteomes, tissue proteomes, and interaction proteomes as well dilute secretomes. The findings presents practical, sensitive cost-effective method.
Abstract not available.