A5051036309- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Calcium signaling and nucleotide metabolism
- Heat shock proteins research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- Lysosomal Storage Disorders Research
- Animal Virus Infections Studies
- Genetics and Neurodevelopmental Disorders
- Peptidase Inhibition and Analysis
- Enzyme Structure and Function
- Biofuel production and bioconversion
- Cell death mechanisms and regulation
- RNA modifications and cancer
- Advanced Glycation End Products research
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- Fungal and yeast genetics research
- RNA regulation and disease
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
University Medical Center Groningen
2017-2023
University of Groningen
2017-2023
University of Freiburg
2019-2023
University Medical Center Utrecht
2017
University of Copenhagen
2008-2016
CoVs have long been regarded as relatively harmless pathogens for humans. Severe respiratory tract infection outbreaks caused by severe acute syndrome CoV and Middle East CoV, however, high pathogenicity mortality rates in These highlighted the relevance of being able to control infections. We used a model MHV, investigate importance recruitment N protein, central component virions, intracellular platforms where replicate, transcribe, translate their genomes. By identifying principal binding...
Autophagy is a catabolic process during which cytosolic material enwrapped in newly formed double-membrane structure called the autophagosome, and subsequently targeted for degradation lytic compartment of cell. The fusion autophagosomes with tightly regulated step involves membrane-bound SNARE proteins. These play crucial role as they promote lipid mixing opposing membranes. Among proteins implicated autophagy, essential protein YKT6 only that evolutionarily conserved from yeast to humans....
The ubiquitin-proteasome system is the major pathway for protein degradation in eukaryotic cells. Proteins to be degraded are conjugated ubiquitin chains that act as recognition signals 26S proteasome. proteasome subunits Rpn10 and Rpn13 known bind ubiquitin, but genetic biochemical data suggest existence of at least one other substrate receptor. Here, we show phylogenetically conserved subunit Dss1 (Sem1) binds linked by K63 K48. Atomic resolution disordered binding sites characterized...
The biogenesis of autophagosomes depends on the conjugation Atg8-like proteins with phosphatidylethanolamine. Atg8 processing by cysteine protease Atg4 is required for its covalent linkage to phosphatidylethanolamine, but it also necessary deconjugation from this lipid release membranes. How these two cleavage steps are coordinated unknown. Here we show that phosphorylation Atg1 inhibits function, an event appears exclusively occur at site autophagosome biogenesis. These results consistent a...
Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into virions. CoV proteins form oligomers but mechanism relevance underlying multimerization remain be fully understood. Using in vitro pull-down experiments density glycerol gradients, we found that at least 3 regions distributed over its entire length mediate self-interaction of mouse hepatitis virus (MHV) severe acute respiratory syndrome coronavirus...
Cells are regularly exposed to stress conditions that may lead protein misfolding. To cope with this challenge, molecular chaperones selectively target structurally perturbed proteins for degradation via the ubiquitin-proteasome pathway. In mammals co-chaperone BAG-1 plays an important role in system. has two orthologues, Bag101 and Bag102, fission yeast Schizosaccharomyces pombe. We show both Bag102 interact 26S proteasomes Hsp70. By epistasis mapping we identify a mutant conserved...
Autophagy is initiated by the formation of phagophore assembly sites (PAS), precursors autophagosomes. In mammals, PAS form throughout cytosol in specialized subdomains endoplasmic reticulum (ER). yeast, also generated close to ER, but always vicinity vacuole. How anchored vacuole and functional significance this localization are unknown. Here, we investigated role PAS-vacuole connection for bulk autophagy yeast. We show that Vac8 constitutes a vacuolar tether stably anchors autophagosome...
Autophagy mediates the degradation of cytoplasmic material. Upon autophagy induction, autophagosomes form a sealed membrane around cargo and fuse with lytic compartment to release for degradation. In order avoid premature fusion immature autophagosomal membranes compartment, this process needs be tightly regulated. Several factors mediating autophagosome-vacuole have recently been identified. budding yeast, requires R-SNARE Ykt6 on autophagosome, together three Q-SNAREs Vam3, Vam7, Vti1...
A mutation, L166P, in the cytosolic protein, PARK7/DJ-1, causes protein misfolding and is linked to Parkinson disease. Here, we identify fission yeast Sdj1 as orthologue of DJ-1 calculate by silico saturation mutagenesis effects point mutants on its structural stability. We also map degradation pathways for Sdj1-L169P, disease-causing L166P protein. Sdj1-L169P forms inclusions, which are enriched Hsp104 disaggregase. Hsp70-type chaperones required efficient Sdj1-L169P. This depends...
Autophagy is a key process in eukaryotes to maintain cellular homeostasis by delivering components lysosomes/vacuoles for degradation and reuse of the resulting metabolites. Membrane rearrangements trafficking events are mediated core machinery autophagy-related (Atg) proteins, which carry out variety functions. How Atg9, lipid scramblase only conserved transmembrane protein within this Atg machinery, trafficked during autophagy remained largely unclear. Here, we addressed question yeast...
The 26S proteasome is a large proteolytic particle present in the cytosol and nucleus of eukaryotic cells. Most intracellular proteins, including those affected by oxidative damage, are degraded proteasome. human thioredoxin, Txnl1, known to associate with thereby equips proteasomes redox capabilities. Here, we characterize fission yeast orthologue called Txl1. Txl1 associates via its C-terminal domain. This domain also found uncharacterized protein, Txc1, which was interact proteasomes. A...
Proteasomes must remove regulatory molecules and abnormal proteins throughout the cell, but how proteasomes can do so efficiently remains unclear. We have isolated a subunit of Arp2/3 complex, Arc3, which binds proteasomes. When overexpressed, Arc3 rescues phenotypes associated with proteasome deficiencies; when its expression is repressed, deficiencies intensify. best known for regulating membrane dynamics vesicular transport; thus, we performed photobleaching experiments showed that are...
The protein known as p97 or VCP in mammals and Cdc48 yeast is a versatile ATPase complex involved several biological functions including membrane fusion, folding, activation of membrane-bound transcription factors. In addition, plays central role degradation misfolded secretory proteins via the ER-associated pathway. This functional diversity depends on its association with various cofactors, to further our understanding function it important that these cofactors are identified analyzed....
In mammalian cells, ASPL is involved in insulin-stimulated redistribution of the glucose transporter GLUT4 and assembly Golgi apparatus. Its putative yeast orthologue, Ubx4, important for proteasome localization, endoplasmic reticulum-associated protein degradation (ERAD), UV-induced RNA polymerase.Here, we show that a cofactor hexameric ATPase complex, known as p97 or VCP mammals Cdc48 yeast. addition, interacts vitro with NSF, another complex. localizes to ER membrane. The central area...
Here a brief introduction to the series is given, which highlights concepts, recent findings and current challenges in understanding chaperone function quality control of proteins.