A5044786511- Viral-associated cancers and disorders
- Histiocytic Disorders and Treatments
- Lymphoma Diagnosis and Treatment
- NF-κB Signaling Pathways
- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Melanoma and MAPK Pathways
- interferon and immune responses
- Parvovirus B19 Infection Studies
- Protein Kinase Regulation and GTPase Signaling
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- T-cell and Retrovirus Studies
- Angiogenesis and VEGF in Cancer
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Protein Tyrosine Phosphatases
- Mathematical Biology Tumor Growth
- Vascular Tumors and Angiosarcomas
- Genetics, Aging, and Longevity in Model Organisms
- Glutathione Transferases and Polymorphisms
- HIV Research and Treatment
- Bioinformatics and Genomic Networks
- Eosinophilic Disorders and Syndromes
- Atherosclerosis and Cardiovascular Diseases
Helmholtz Zentrum München
2009-2024
German Center for Infection Research
2016-2024
Center for Environmental Health
2022
Institute for Environment and Human Security
2003-2008
Institut für Medizinische Informatik, Biometrie und Epidemiologie
2003
Amt für Umwelt
2000
Urologische Klinik München
1995-1996
National Institutes of Health
1995
National Cancer Institute
1995
University of Freiburg
1994
Abstract Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1’s transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 role in signalling remains elusive. Here we demonstrate that interacts directly with a binding motif within CTAR2. Functional NMR studies supported molecular modeling...
Abstract Non-protein-coding RNAs are a functionally versatile class of transcripts exerting their biological roles on the RNA level. Recently, we demonstrated that vault complex-associated (vtRNAs) significantly upregulated in Epstein–Barr virus (EBV)-infected human B cells. Very little is known about function(s) vtRNAs or complex. Here, individually express latent EBV-encoded proteins cells and identify membrane protein 1 (LMP1) as trigger for vtRNA upregulation. Ectopic expression...
The K15 gene of Kaposi's sarcoma-associated herpesvirus (also known as human 8) consists eight alternatively spliced exons and has been predicted to encode membrane proteins with a variable number transmembrane regions common C-terminal cytoplasmic domain putative binding sites for SH2 SH3 domains, well tumor necrosis factor receptor-associated factors. These features are reminiscent the latent LMP-1 LMP2A Epstein-Barr virus and, more distantly, STP, Tip, Tio related gamma(2)-herpesviruses...
The tumor necrosis factor-receptor-associated factor 2 (TRAF2)- and Nck-interacting kinase (TNIK) is a ubiquitously expressed member of the germinal center family. TNIK functions in hematopoietic cells role TNIK-TRAF interaction remain largely unknown. By functional proteomics we identified as partner latent membrane protein 1 (LMP1) signalosome primary human B-cells infected with Epstein-Barr virus (EBV). RNAi-mediated knockdown proved critical for canonical NF-κB c-Jun N-terminal (JNK)...
The CD154–CD40 receptor complex plays a pivotal role in several inflammatory pathways. Attempts to inhibit the formation of this have resulted systemic side effects. Downstream inhibition CD40 signaling pathway therefore seems better way ameliorate disease. To relay signal, recruits adapter proteins called tumor necrosis factor receptor-associated factors (TRAFs). CD40–TRAF6 interactions are known play an essential diseases. We used silico, vitro, and vivo experiments identify characterize...
Obesity and type 2 diabetes (T2D) are growing health challenges with unmet treatment needs. Traf2- NCK-interacting protein kinase (TNIK) is a recently identified obesity- T2D-associated gene unknown functions. We show that TNIK governs lipid glucose homeostasis in Drosophila mice. Loss of the ortholog TNIK, misshapen, altered metabolite profiles impaired de novo lipogenesis high sugar-fed larvae. Tnik knockout mice exhibited hyperlocomotor activity were protected against diet-induced fat...
The tumor necrosis factor (TNF)-receptor 1-associated death domain protein (TRADD) mediates induction of apoptosis as well activation NF-kappaB by cellular TNF-receptor 1 (TNFR1). TRADD is also recruited the latent membrane (LMP1) oncoprotein Epstein-Barr virus, but its role in LMP1 signaling has remained enigmatic. In human B lymphocytes, we have generated, to our knowledge, first genetic knockout investigate TRADD's signal transduction. Our data from TRADD-deficient cells demonstrate that...
Besides inducing apoptosis, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates NF-κB. The apoptosis signaling pathway of TRAIL is well characterized involving receptors, Fas-associated protein with death domain (FADD) and caspase-8. In contrast, the molecular mechanism to NF-κB remains controversial. Here, we receptor–proximal mediators activation by TRAIL. Deletion DD receptors 1 2 revealed that it essential in signaling. Because FADD interacts receptor DD, was...
Using immobilized GST-Raf-1 as bait, we have isolated the intermediate filament protein vimentin a Raf-1-associated protein. Vimentin coimmunoprecipitated and colocalized with Raf-1 in fibroblasts. was not substrate, but phosphorylated by kinases. We provide evidence for at least two kinases identified one casein kinase 2. They are regulated Raf-1, since activation status of correlated phosphorylation vimentin. preparations interfered its polymerization vitro. A subset tryptic...
Abstract IκB kinase 2 (IKK2) is well known for its pivotal role as a mediator of the canonical NF-κB pathway, which has important functions in inflammation and immunity, but also cancer. Here we identify novel critical function IKK2 co-factor NEMO activation oncogenic c-Jun N-terminal (JNK) signaling, induced by latent membrane protein 1 (LMP1) Epstein-Barr virus (EBV). Independent activity, TGFβ-activated (TAK1) mediates LMP1 signaling complex formation, ubiquitination subsequent...
ABSTRACT Epstein-Barr virus (EBV) infects human resting B cells and transforms them in vitro into continuously growing lymphoblastoid cell lines (LCLs). EBV nuclear antigen 2 (EBNA2) is one of the first viral proteins expressed after infection. It able to transactivate as well cellular target genes by interaction with transcription factors. EBNA2 can be studied easily using an LCL (ER/EB2-5) which wild-type replaced estrogen-inducible EBNA2. Since surface molecule CD83, a member...
Tetherin (or BST-2) is an antiviral host restriction factor that suppresses the release of HIV-1 and other enveloped viruses by tethering them to cell surface. Recently, it has been demonstrated tetherin also acts as innate sensor assembly induces NF-κB-dependent proinflammatory responses. Furthermore, reported polymorphisms in promoter 3' untranslated region bst2 gene may affect clinical outcome infection. However, non-synonymous open reading frame have not yet described or functionally...
Raf kinases are regulators of cellular proliferation, transformation, differentiation, and apoptosis. To identify downstream targets Raf-1 in vivo, we used NIH 3T3 fibroblasts expressing a kinase domain-estrogen receptor fusion protein (BXB-ER), whose activity can be acutely regulated by estrogen. Proteins differentially phosphorylated 20 min after BXB-ER activation living cells were displayed two-dimensional electrophoresis. The with the most prominent newly induced phosphorylation was...
We have identified protein kinase C-zeta (PKC-zeta) as a novel suppressor of neoplastic transformation caused by the v-raf oncogene. PKC-zeta overexpression drastically retards proliferation, abolishes anchorage-independent growth, and reverts morphological v-raf-transformed NIH-3T3 cells. The molecular basis for this effect appears to be specific induction junB egr-1 expression, triggered synergistically via Raf/Mek/MAPK-independent mechanism v-raf. junB-promoter/CAT assays revealed that...
The actin-bundling protein Fascin (FSCN1) is a tumor marker that highly expressed in numerous types of cancer including lymphomas and important for migration metastasis cells. has also been detected B lymphocytes are freshly-infected with Epstein-Barr virus (EBV), however, both the inducers mechanisms upregulation still unclear. Here we show EBV-encoded oncoprotein latent membrane 1 (LMP1), potent regulator cellular signaling transformation, sufficient to induce mRNA lymphocytes. expression...