A5048718944- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Neuroscience and Neuropharmacology Research
- Microbial Natural Products and Biosynthesis
- Microbial Metabolism and Applications
- Extracellular vesicles in disease
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Plant responses to water stress
- Plant biochemistry and biosynthesis
- Mosquito-borne diseases and control
- Phytochemistry and biological activity of medicinal plants
- ATP Synthase and ATPases Research
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Tea Polyphenols and Effects
- Genomics, phytochemicals, and oxidative stress
- Tannin, Tannase and Anticancer Activities
- PI3K/AKT/mTOR signaling in cancer
- Photosynthetic Processes and Mechanisms
- Ferroptosis and cancer prognosis
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- NF-κB Signaling Pathways
Heinrich Heine University Düsseldorf
2016-2021
Düsseldorf University Hospital
2019-2021
Abstract Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently mTORC1, activate other kinases mTOR network. To delineate aa-stimulated network dynamics, we here combine computational–experimental approach text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK),...
Abstract Ferroptosis is a form of regulated cell death that emerges to be relevant for therapy-resistant and dedifferentiating cancers. Although several lines evidence suggest ferroptosis type autophagy-dependent death, the underlying molecular mechanisms remain unclear. Fin56, 3 inducer, triggers by promoting glutathione peroxidase 4 (GPX4) protein degradation via not fully understood pathway. Here, we determined Fin56 induces autophagy in bladder cancer cells Fin56-triggered...
Macroautophagy/autophagy and necroptosis represent two opposing cellular s tress responses. Whereas autophagy primarily fulfills a cyto-protective function, is form of regulated cell death induced via receptors. Here, we aimed at investigating the molecular crosstalk between these pathways. We observed that RIPK3 directly associates with AMPK phosphorylates its catalytic subunit PRKAA1/2 T183/T172. Activated then autophagy-regulating proteins ULK1 BECN1. However, lysosomal degradation...
Autophagy, apoptosis, and necroptosis are stress responses governing the ultimate fate of a cell. However, crosstalk between these cellular is not entirely understood. Especially, it clear whether autophagy-initiating kinase ULK1 cell-death-regulating RIPK1 involved in this potential crosstalk. Here, we identify as substrate ULK1. ULK1-dependent phosphorylation reduces complex IIb/necrosome assembly tumor necrosis factor (TNF)-induced cell death, whereas deprivation enhances TNF-induced...
Macroautophagy/autophagy is an evolutionarily conserved cellular process whose induction regulated by the ULK1 protein kinase complex. The subunit ATG13 functions as adaptor recruiting ULK1, RB1CC1 and ATG101 to a core Furthermore, directly binds both phospholipids members of Atg8 family. central involvement in complex formation makes it attractive target for autophagy regulation. Here, we analyzed known interactions with proteins lipids their potential modulation induction. Targeting...
Cisplatin-based regimens are routinely employed for the treatment of urothelial carcinoma. However, therapeutic success is hampered by primary presence or development cisplatin resistance. This chemoresistance executed multiple cellular pathways. In recent years, process autophagy has been identified as a prosurvival pathway cancer cells. On one hand, enables cells to survive conditions low oxygen nutrient supply, frequently found in tumors. other supports Here, we aimed at investigating...
Abstract The protein kinase TBK1 is a central regulator of innate immune responses and autophagy, ablation either function has been linked to neuroinflammatory or degenerative diseases. Autophagy an intracellular process that recycles old damaged proteins organelles. In recent years, the TBK1-dependent regulation autophagy pathways characterized. However, autophagy-dependent activity awaits further clarification. Here, we observed recruited SQSTM1/p62-containing aggregates via selective...
Abstract Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, buffering cytosolic Ca 2+ initiation apoptosis. Compounds that interfere these termed mitochondrial toxins, many which derived from microbes, such as antimycin A, oligomycin ionomycin. Here, we identify mycotoxin phomoxanthone A (PXA), endophytic fungus Phomopsis longicolla , a toxin. We show PXA elicits strong release mitochondria but not ER. In addition, depolarises similarly to...
Abstract In rodents, gene‐expression, neuronal tuning, connectivity and neurogenesis studies have postulated that the dorsal, intermediate ventral hippocampal formation (HF) are distinct entities. These findings underpinned by behavioral showing a dissociable role of dorsal HF in learning, memory, stress emotional processing. However, up to now, molecular basis such differences relation discrete boundaries is largely unknown. Therefore, we analyzed binding site densities for glutamatergic...
Cisplatin-based treatment is the standard of care therapy for urothelial carcinomas. However, complex cisplatin resistance mechanisms limit success this approach. Both apoptosis and autophagy have been shown to contribute resistance. Prodigiosin, a secondary metabolite from various bacteria, exerts different biological activities including modulation these two cellular stress response pathways. We analyzed effect prodigiosin on protein levels autophagy- apoptosis-related proteins in...
Abstract Autophagy is an intracellular recycling pathway with implications for homeostasis and cell survival. Its pharmacological modulation can aid chemotherapy by sensitizing cancer cells toward approved drugs overcoming chemoresistance. Recent translational data on autophagy modulators show promising results in reducing tumor growth metastasis, but also reveal a need more specific compounds novel lead structures. Here, we searched such autophagy-modulating flow cytometry-based...
Phomoxanthone A, a bioactive xanthone dimer isolated from the endophytic fungus Phomopsis sp., is mitochondrial toxin weakening cellular respiration and electron transport chain activity by fast breakup of assembly. Here, multi-disciplinary strategy has been developed applied for identifying phomoxanthone A target(s) to fully address its mechanism action, based on drug affinity response target stability targeted limited proteolysis. Both approaches point identification carbamoyl-phosphate...