A5009617104- Cervical Cancer and HPV Research
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- RNA Research and Splicing
- Virus-based gene therapy research
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- interferon and immune responses
- Hepatitis B Virus Studies
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Genomics and Chromatin Dynamics
- Herpesvirus Infections and Treatments
- Carcinogens and Genotoxicity Assessment
- Immunotherapy and Immune Responses
- Bacteriophages and microbial interactions
- Cancer Research and Treatments
- HIV/AIDS drug development and treatment
- Folate and B Vitamins Research
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Gut microbiota and health
- Peptidase Inhibition and Analysis
- T-cell and Retrovirus Studies
Biotechnologie et Signalisation Cellulaire
2002-2025
École Supérieure de Biotechnologie de Strasbourg
2013-2025
Université de Strasbourg
2006-2025
Centre National de la Recherche Scientifique
2006-2025
Institut de Biologie Moléculaire et Cellulaire
2018
École Normale Supérieure - PSL
2005-2012
European Molecular Biology Laboratory
2001-2011
European Molecular Biology Laboratory
2001-2008
Helmholtz Zentrum München
2008
Technical University of Munich
2008
E6 viral oncoproteins are key players in epithelial tumors induced by papillomaviruses vertebrates, including cervical cancer humans. proteins target many host specifically interacting with acidic LxxLL motifs. We solved the crystal structures of bovine (BPV1) and human (HPV16) papillomavirus bound to peptides from focal adhesion protein paxillin ubiquitin ligase E6AP, respectively. In both proteins, two zinc domains a linker helix form basic-hydrophobic pocket, which captures helical motifs...
During spliceosome assembly, splicing factor 1 (SF1) specifically recognizes the intron branch point sequence (BPS) UACUAAC in pre-mRNA transcripts. We show that KH-QUA2 region of SF1 defines an enlarged KH (hn RNP K) fold which is necessary and sufficient for BPS binding. The 3′ part (UA A C), including conserved adenosine (underlined), recognized a hydrophobic cleft formed by Gly-Pro-Arg-Gly motif variable loop domain. QUA2 5′ nucleotides (ACU). acting as nucleophile first biochemical step...
Discrimination between splice sites and similar, nonsplice sequences is essential for correct intron removal messenger RNA formation in eukaryotes. The 65- 35-kD subunits of the splicing factor U2AF, U2AF 65 35 , recognize, respectively, pyrimidine-rich tract conserved terminal AG present at metazoan 3′ sites. We report that DEK, a chromatin- RNA-associated protein mutated or overexpressed certain cancers, enforces site discrimination by U2AF. DEK phosphorylated serines 19 32 associates with...
Significance The splicing of human pre-mRNAs is tightly controlled and regulated during the assembly spliceosome onto pre-mRNA introns. Recognition regulatory RNA sequence motifs by factors an essential early step assembly. We combine single-pair FRET NMR to show that recognition 3′ splice site in introns heterodimeric factor U2 auxiliary (U2AF) involves conformational dynamics population shifts its binding domains between open closed conformations. Unexpectedly, small subunit U2AF35...
The HPV E6 oncoprotein maintains the malignant phenotype of HPV-positive cancer cells and represents an attractive therapeutic target. forms a complex with cellular E6AP ubiquitin ligase, ultimately leading to p53 degradation. recently elucidated x-ray structure HPV16 E6/E6AP showed that distinct binding pocket for E6AP. This discovery raises question whether is druggable, i. e. it provides docking site functional inhibitors. To address these issues, we performed detailed analysis...
ABSTRACT ΔNp73α is a major oncogenic isoform of tumor suppressor p73. Here, we report protein-binding partners in the organelle and cytoplasmic compartments cellular model consisting human keratinocytes transformed by E6 E7 oncoproteins β-HPV38 virus associated with non-melanoma skin cancer.
ABSTRACT Papillomaviruses (PVs) are a large family of small DNA viruses infecting mammals, reptiles, and birds. PV infection induces cell proliferation that may lead to the formation orogenital or skin tumors. PV-induced has been related mainly expression two oncoproteins, E6 E7. In mammalian PVs, contains 70-residue zinc-binding repeats, whereas E7 consists natively unfolded N-terminal region followed by domain which folds as an obligate homodimer. Here, we show both novel francolin bird...
All RNA sequences that fold into hairpins possess the intrinsic potential to form intermolecular duplexes because of their high self-complementarity. The thermodynamically more stable duplex conformation is favored under salt conditions and at concentrations, posing a challenging problem for structural studies small hairpin conformations. We developed applied novel approach unambiguously distinguish conformations analysis Xist A-repeat. Using combination quantitative HNN-COSY experiment an...
Human papillomavirus type 16 (HPV16) and other oncoviruses have been shown to block innate immune responses persist in the host. However, avoid viral persistence, response attempts clear infection. IL-1β is a powerful cytokine produced when motifs are sensed by receptors that members of inflammasome family. Whether such as HPV16 can activate pathway remains unknown. Here, we show infection human keratinocytes with induced secretion IL-1β. Yet, upon expression early genes, transcription was...
Expression of replication-dependent histone genes requires a conserved hairpin RNA element in the 3′ untranslated regions poly(A)-less mRNAs. The is recognized by hairpin-binding protein or stem-loop-binding (HBP/SLBP). This protein–RNA interaction important for endonucleolytic cleavage generating mature mRNA end. and presumably HBP/SLBP are also required nucleo-cytoplasmic transport, translation, stability processing both regulated during cell cycle. Here, we have determined...
Modified nucleosides play an important role in structure and function of tRNA. We have determined the solution anticodon stem–loop (ASL) initiator tRNA Schizosaccharomyces pombe . The incorporation N6 -threonylcarbamoyladenosine at position 3′ to triplet (t 6 A37) results formation a U-turn motif enhances stacking interactions within loop stem regions (i.e. between A35 t by bulging out U36. This conformation was not observed crystal tRNAi including same modification its loop, nor unmodified...
Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer and other malignancies in humans. The HPV E6 oncoprotein is considered to be an attractive therapeutic target since its inhibition can lead the apoptotic cell death HPV-positive cells. type 16 (HPV16) E6-binding peptide pep11, variants thereof, induce specifically HPV16-positive Although they do not encompass LxxLL binding motif found cellular HPV16 interaction partners, such as E6AP, pep11 strongly bind by contacting...
The beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, beta-3 appears be more highly represented mucosal epithelia than Functional studies have also highlighted that HPV49 shares some functional similarities with high-risk (HR) HPV16. Here, we describe characterization of