A5034046190- Ubiquitin and proteasome pathways
- interferon and immune responses
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- NF-κB Signaling Pathways
- Advanced biosensing and bioanalysis techniques
- Immune Response and Inflammation
- History and Developments in Astronomy
- Enzyme Structure and Function
- ATP Synthase and ATPases Research
- T-cell and B-cell Immunology
- Neuroinflammation and Neurodegeneration Mechanisms
- Heat shock proteins research
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Redox biology and oxidative stress
- Genomic variations and chromosomal abnormalities
- vaccines and immunoinformatics approaches
- Endoplasmic Reticulum Stress and Disease
- Cytokine Signaling Pathways and Interactions
Friedrich Miescher Institute
2018-2024
University of Freiburg
2011-2017
Protein modification by the ubiquitin-like protein ISG15 is an interferon (IFN) effector system, which plays a major role in antiviral defense. counteracted isopeptidase USP18, negative regulator of IFN signaling, was also shown to exert its regulatory function isopeptidase-independent manner. To dissect enzymatic and nonenzymatic functions USP18 vivo, we generated knock-in mice (USP18(C61A/C61A)) expressing enzymatically inactive USP18. USP18(C61A/C61A) displayed increased levels...
Protein modification by interferon‐stimulated gene 15 (ISG15), an ubiquitin‐like modifier, affects multiple cellular functions and represents one of the major antiviral effector systems. Covalent linkage ISG15 to proteins was previously reported be counteracted ubiquitin‐specific protease 18 (USP18). To date, analysis molecular properties USP18 hampered low expression yields impaired solubility. We established high‐yield in insect cells purified homogeneity. binds with high affinity ISG15,...
The cullin-4-based RING-type (CRL4) family of E3 ubiquitin ligases functions together with dedicated substrate receptors. Out the ˜29 CRL4 receptors reported, DDB1- and CUL4-associated factor 1 (DCAF1) is essential for cellular survival growth, its deregulation has been implicated in tumorigenesis. We carried out biochemical structural studies to examine structure mechanism CRL4DCAF1 ligase. In 8.4 Å cryo-EM map , four CUL4-RBX1-DDB1-DCAF1 protomers are organized into two dimeric...
Retrotransposon control in mammals is an intricate process that effectuated by a broad network of chromatin regulatory pathways. We previously discovered ChAHP, protein complex with repressive activity against short interspersed element (SINE) retrotransposons composed the transcription factor ADNP, remodeler CHD4, and HP1 proteins. Here we identify ChAHP2, homologous to which ADNP replaced ADNP2. ChAHP2 predominantly targeted endogenous retroviruses (ERVs) long elements (LINEs) via...
Abstract Background Covalent linkage of the ubiquitin-like protein ISG15 interferes with viral infection and USP18 is major protease which specifically removes from target proteins. Thus, boosting modification by inhibition might represent a new strategy to interfere replication. However, so far no heterologous expression system was available yield sufficient amounts catalytically active for high-throughput based inhibitor screens. Results High-level achieved applying chaperone-based fusion...
ABSTRACT Retrotransposon control in mammals is an intricate process that effectuated by a broad network of chromatin regulatory pathways. We previously discovered ChAHP, protein complex with repressive activity against SINE retrotransposons, composed the transcription factor ADNP, remodeler CHD4, and HP1 proteins. Here we identify ChAHP2, homologous to wherein ADNP replaced ADNP2. ChAHP2 predominantly targeted ERVs LINEs, via HP1β-mediated binding H3K9 trimethylated histones. further...