Michael Naumann
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View article: Discovery of chromatin-based determinants of azacytidine and decitabine anti-cancer activity
Discovery of chromatin-based determinants of azacytidine and decitabine anti-cancer activity Open
The DNA-incorporating nucleoside analogs azacytidine (AZA) and decitabine (DEC) have clinical efficacy in blood cancers, yet the precise mechanism by which these agents kill cancer cells has remained unresolved -- specifically, whether the…
CYLD-TRAF6 interaction promotes ADP-heptose-induced NF-κB signaling in H. pylori infection Open
The inflammatory response associated with Helicobacter pylori ( H. pylori ) infection causes a multitude of alterations in the gastric microenvironment, leading to the slow and steady disruption of the gastric epithelial barrier. Activatio…
<span>ALPK1</span> ‐Dependent <span>cIAP1</span> Degradation Regulates <span> <i>Helicobacter pylori</i> </span> ‐Induced Apoptosis Open
Helicobacter pylori infection poses a significant risk for disrupting the gastric epithelium by inducing inflammation and apoptosis. Here, we identify alpha kinase 1 (ALPK1) as essential in H. pylori ‐induced apoptosis. The absence of ALPK…
CSN-CRL Complexes: New Regulators of Adipogenesis Open
Recent discoveries revealed mechanistic insights into the control of adipogenesis by the Constitutive Photomorphogenesis 9 Signalosome (CSN) and its variants, CSNCSN7A and CSNCSN7B, which differ in the paralog subunits, CSN7A and CSN7B. CS…
The enigma of maladaptation in gastric pathophysiology Open
Despite a decline in global incidence, gastric cancer (GC) remains a major health concern. The development of GC is a sequential, multistage maladaptive process involving numerous different factors. Understanding the complexity of GC devel…
Dysregulation of deubiquitinylases: a linchpin of gastrointestinal diseases Open
Ubiquitinylation of proteins regulates manifold processes and is reversed by deubiquitinylating enzymes (DUBs), which are therefore implicated in a plethora of cellular processes. DUBs are frequently upregulated in many diseases, while in …
Ablation of the deubiquitinating enzyme cylindromatosis (CYLD) augments STAT1-mediated M1 macrophage polarization and fosters Staphylococcus aureus control Open
In atopic dermatitis (AD), lesional skin is frequently colonized by Staphylococcus aureus , which promotes clinical symptoms of the disease. The inflammatory milieu in the skin is characterized by a Th2 response, including M2 macrophages, …
Activation and Reactivity of the Deubiquitinylase OTU Cezanne-2 from MD Simulations and QM/MM Calculations Open
Cezanne-2 (Cez2) is a deubiquitinylating (DUB) enzyme involved in the regulation of ubiquitin-driven cellular signaling and selectively targets Lys11-linked polyubiquitin chains. As a representative member of the ovarian tumor (OTU) subfam…
Differential expression of the ubiquitin-editing enzyme A20 in gastric biopsies indicates the severity of disease Open
A20, an ubiquitin-editing enzyme, plays a pivotal role in regulating cell signaling and immune responses. Dysregulated A20 expression has been associated with various pathological conditions, including inflammatory diseases and malignancie…
Harnessing gastrointestinal organoids for cancer therapy Open
Gastrointestinal organoids have emerged as a model system that authentically recapitulates the in vivo situation. Despite biomedical and technical challenges, self-assembled 3D structures derived from pluripotent stem cells or healthy and …
View article: Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma
Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma Open
Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation f…
View article: Synthesis and structure–activity relationships of USP48 deubiquitinylase inhibitors
Synthesis and structure–activity relationships of USP48 deubiquitinylase inhibitors Open
Ubiquitin‐specific proteases represent a family of enzymes that catalyze the cleavage of ubiquitin from specific substrate proteins to regulate their activity. USP48 is a rarely studied USP, which has recently been linked to inflammatory s…
Latent CSN-CRL complexes are crucial for curcumin-induced apoptosis and recruited during adipogenesis to lipid droplets via small GTPase RAB18 Open
The COP9 signalosome (CSN) and cullin-RING ubiquitin ligases (CRLs) form latent CSN-CRL complexes detectable in cells. We demonstrate that the CSN variants CSNCSN7A and CSNCSN7B preferentially bind to CRL3 or CRL4A and CRL4B, respectively.…
Structural Dynamics of Lys11-Selective Deubiquitinylase Cezanne-1 during the Catalytic Cycle Open
Deubiquitinylating enzymes (DUBs) regulate the deubiquitinylation process of post-translationally modified proteins and thus control protein signaling in various cellular processes. The DUB Cezanne-1 catalyzes the cleavage of the iso-pepti…
Helicobacter pylori regulates TIFA turnover in gastric epithelial cells. Open
The human pathogen Helicobacter pylori induces a strong inflammatory response in gastric mucosa manifested by the recruitment of neutrophils and macrophages to the places of infection, and by changes in epithelial integrity and function. A…
Matrix Metalloproteinases in Helicobacter pylori–Associated Gastritis and Gastric Cancer Open
Gastric cancer is one of the leading causes of the cancer-related mortality worldwide. The etiology of this disease is complex and involves genetic predisposition and environmental factors, including Helicobacter pylori. Infection of the s…
A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection Open
A hallmark of infection by the pathogen Helicobacter pylori , which colonizes the human gastric epithelium, is the simultaneous activation of the classical and alternative nuclear factor kappa-light-chain-enhancer of activated B cells (NF-…
Helicobacter pylori-induced reactive oxygen species direct turnover of CSN-associated STAMBPL1 and augment apoptotic cell death Open
Deubiquitinylases (DUBs) are central regulators of the ubiquitin system involved in protein regulation and cell signalling and are important for a variety of physiological processes. Most DUBs are cysteine proteases, and few other protease…
View article: Importance of cortactin for efficient epithelial NF-ĸB activation by Helicobacter pylori, Salmonella enterica and Pseudomonas aeruginosa, but not Campylobacter spp.
Importance of cortactin for efficient epithelial NF-ĸB activation by Helicobacter pylori, Salmonella enterica and Pseudomonas aeruginosa, but not Campylobacter spp. Open
Transcription factors of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF-ĸB) family control important signaling pathways in the regulation of the host innate immune system. Various bacterial pathogens in the human ga…
<span>Substrate‐assisted</span> activation and selectivity of the bacterial <span>RavD</span> effector deubiquitinylase Open
Deubiquitinylases (DUBs) catalyze the peptide bond cleavage of specific ubiquitin linkages at distinct protein substrates. Pathogens from viruses and bacteria independently developed effector proteins with DUB activity to mimic host DUB fu…