A5001699371- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Peptidase Inhibition and Analysis
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Cardiac electrophysiology and arrhythmias
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- HIV/AIDS drug development and treatment
- Cancer-related gene regulation
- Nuclear Structure and Function
- Genetics, Bioinformatics, and Biomedical Research
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
Max Planck Institute of Biochemistry
2021-2024
University of Vienna
2016-2021
Max Perutz Labs
2016-2021
Vienna Biocenter
2017-2021
The C-terminal domain (CTD) of the largest subunit RNA polymerase II (Pol II) is a regulatory hub for transcription and processing. Here, we identify PHD-finger protein 3 (PHF3) as regulator mRNA stability that docks onto Pol CTD through its SPOC domain. We characterize reader preferentially binds two phosphorylated Serine-2 marks in adjacent repeats. PHF3 drives liquid-liquid phase separation II, colocalizes with clusters tracks across length genes. knock-out or deletion human cells results...
Abstract An emerging mechanism of ubiquitylation involves partnering two distinct E3 ligases. In the best-characterized E3-E3 pathways, ARIH-family RING-between-RING (RBR) E3s ligate ubiquitin to substrates neddylated cullin-RING E3s. The ARIH2 has been implicated in CUL5-RBX2-based E3s, including APOBEC3-family host hijacked by HIV-1 virion infectivity factor (Vif). However, structural mechanisms remained elusive. Here and biochemical analyses reveal distinctive autoinhibition, activation...
Poly(ADP-ribose) glycohydrolase (PARG) regulates cellular poly(ADP-ribose) (PAR) levels by rapidly cleaving glycosidic bonds between ADP-ribose units. PARG interacts with proliferating cell nuclear antigen (PCNA) and is strongly recruited to DNA damage sites in a PAR- PCNA-dependent fashion. Here we identified acetylation site K409 that essential for its interaction PCNA, localization within replication foci recruitment sites. We found be part of non-canonical PIP-box the disordered...
ABSTRACT Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase known to regulate microtubule dynamics and cell cycle progression. SIRT2 has also been implicated in the pathology of cancer, neurodegenerative diseases progeria. Here, we show that depletion or overexpression causes nuclear envelope reassembly defects. We link this phenotype recently identified regulator ANKLE2. ANKLE2 acetylation at K302 phosphorylation S662 are dynamically regulated throughout by essential for normal reassembly....
Abstract Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, ‘cullin–RING’ and ‘RBR’, are individually found in several hundred human ligases, collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex RBX1 (also called ROC1), of interest due its tumor suppressive interaction TP53, uniquely encompasses both cullin–RING RBR Here, cryo-EM, biochemistry cellular assays elucidate a 1.8-MDa hexameric CUL9–RBX1...
N-terminal histone tails are subject to many posttranslational modifications that recognized by and interact with designated reader domains in histone-binding proteins. BROMO domain adjacent zinc finger 2B (BAZ2B) is a multidomain protein contains two modules, plant homeodomain (PHD) bromodomain (BRD), linked largely disordered linker. Although previous studies have reported specificity of the PHD for unmodified N terminus H3 BRD acetylated at Lys14 (H3K14ac), exact mode binding BAZ2B its...
SUMMARY The C-terminal domain (CTD) of the largest subunit RNA polymerase II (Pol II) is a regulatory hub for transcription and processing. Here, we identify PHD-finger protein 3 (PHF3) as new CTD-binding factor that negatively regulates mRNA stability. PHF3 SPOC preferentially binds to CTD repeats phosphorylated on Serine-2 tracks with Pol across length genes. competes TFIIS binding through its TFIIS-like (TLD), thus inhibiting TFIIS-mediated rescue backtracked II. knock-out or deletion in...
Protein post-translational modification with ubiquitin (Ub) is a versatile signal regulating almost all aspects of cell biology, and an increasing range diseases associated impaired Ub modification. In this light, the system offers attractive, yet underexplored route to development novel targeted treatments. A promising strategy for small molecule intervention posed by final components enzymatic ubiquitination cascade, E3 ligases, as they determine specificity protein pathway. Here, we...
Abstract Protein post‐translational modification with ubiquitin (Ub) is a versatile signal regulating almost all aspects of cell biology, and an increasing range diseases associated impaired Ub modification. In this light, the system offers attractive, yet underexplored route to development novel targeted treatments. A promising strategy for small molecule intervention posed by final components enzymatic ubiquitination cascade, E3 ligases, as they determine specificity protein pathway. Here,...
T he C-terminal domain (CTD) of the largest subunit RNA polymerase II (Pol II) is a regulatory hub for transcription and processing. Here, we identify PHD-finger protein 3 (PHF3) as new CTD-binding factor that negatively regulates mRNA stability. The PHF3 SPOC preferentially binds to CTD repeats phosphorylated on Serine-2 tracks with Pol across length genes. competes TFIIS binding through its TFIIS-like (TLD), thus inhibiting TFIIS-mediated rescue backtracked II. knock-out or deletion in...