Research
- Research Topics
- Cell Biology and Tumor Biology
- Stem Cells and Cancer
- Inflammatory Stress in Stem Cells
- Experimental Hematology
- Molecular Embryology
- Signal Transduction and Growth Control
- Epigenetics
- Redox Regulation
- Vascular Oncology and Metastasis
- Clinical Neurobiology
- Molecular Neurogenetics
- Molecular Neurobiology
- Mechanisms Regulating Gene Expression
- Molecular Biology of Centrosomes and Cilia
- Dermato-Oncology
- Pediatric Leukemia
- Tumour Metabolism and Microenvironment
- Personalized Medical Oncology
- Molecular Hematology - Oncology
- Cancer Progression and Metastasis
- Translational Surgical Oncology
- Neuronal Signaling and Morphogenesis
- Cell Signaling and Metabolism
- Cell Fate Engineering and Disease Modeling
- Cancer Drug Development
- Cell Morphogenesis and Signal Transduction
- Functional and Structural Genomics
- Molecular Genome Analysis
- Molecular Genetics
- Pediatric Neurooncology
- Cancer Genome Research
- Chromatin Networks
- Functional Genome Analysis
- Theoretical Systems Biology
- Neuroblastoma Genomics
- Signaling and Functional Genomics
- Signal Transduction in Cancer and Metabolism
- RNA-Protein Complexes and Cell Proliferation
- Systems Biology of Signal Transduction
- Areas of Interest
- Advancement of clinical proteomics for systems medicine
- Bridging from the single cell to the cell population – Epo-induced cellular responses and erythroleukemia
- Deciphering tumor microenvironment interactions determining lung cancer development
- Mechanisms controlling the compensation of liver injury and towards model-based biomarkers for early detection of liver cancer
- Application of dynamic pathway modelling for personalized medicine
- Group Members
- Publications
- Open Positions
- Funding
- Teaching
- Areas of Interest
- Molecular thoracic Oncology
- Proteomics of Stem Cells and Cancer
- Computational Genomics and System Genetics
- Applied Functional Genomics
- Applied Bioinformatics
- Translational Medical Oncology
- Metabolic crosstalk in cancer
- Pediatric Glioma Research
- Cancer Epigenomics
- Translational Pediatric Sarcoma Research
- Artificial Intelligence in Oncology
- Mechanisms of Genomic Variation and Data Science
- Neuropathology
- Pediatric Oncology
- Neurooncology
- Somatic Evolution and Early Detection
- Translational Control and Metabolism
- Soft-Tissue Sarcoma
- Precision Sarcoma Research
- Brain Mosaicism and Tumorigenesis
- Mechanisms of Genome Control
- Translational Gastrointestinal Oncology and Preclinical Models
- Translational Lymphoma Research
- Mechanisms of Leukemogenesis
- Genome Instability in Tumors
- Developmental Origins of Pediatric Cancer
- Brain Tumor Translational Targets
- Translational Functional Cancer Genomics
- Regulatory Genomics and Cancer Evolution
- SPRINT
- Cancer Risk Factors and Prevention
- Cancer Epidemiology
- Biostatistics
- Clinical Epidemiology and Aging Research
- Health Economics
- Physical Activity, Prevention and Cancer
- Preventive Oncology
- Personalized Early Detection of Prostate Cancer
- Digital Biomarkers for Oncology
- Tumorigenesis and molecular cancer prevention
- Genomic Epidemiology
- Cancer Survivorship
- Immunology, Infection and Cancer
- Structural Biology of Infection and Immunity
- Cellular Immunology
- B Cell Immunology
- Immune Diversity
- Immunoproteomics
- Personalized Immunotherapy
- mRNA Cancer Immunotherapies
- Tumor Immunology and Tumor Immunotherapy
- Infections and Cancer Epidemiology
- Pathogenesis of Virus-Associated Tumors
- Immunotherapy and Immunoprevention
- Virus-associated Carcinogenesis
- Chronic Inflammation and Cancer
- Microbiome and Cancer
- Molecular Oncology of Gastrointestinal Tumors
- Applied Tumor Immunity
- Neuroimmunology and Brain Tumor Immunology
- Applied Tumor Biology
- Virotherapy
- Adaptive Immunity and Lymphoma
- Dermal Oncoimmunology
- Immune Regulation in Cancer
- Systems Immunology and Single Cell Biology
- Pediatric Immuno-Oncology
- Epithelium Microbiome lnteractions
- Experimental Hepatology, Inflammation and Cancer
- GMP & T Cell Therapy
- Tumorvirus-specific Vaccination Strategies
- Mammalian Cell Cycle Control Mechanisms
- Molecular Therapy of Virus-Associated Cancers
- DNA Vectors
- Episomal-Persistent DNA in Cancer- and Chronic Diseases
- Immune Monitoring
- News
- Imaging and Radiooncology
- Radiology
- Research
- Computational Radiology Research Group
- Contrast Agents In Radiology Research Group
- Neuro-Oncologic Imaging Research Group
- Radiological Early Response Assessment Of Modern Cancer Therapies
- Imaging In Monoclonal Plasma Cell Disorders
- 7 Tesla MRI - Novel Imaging Biomarkers
- Functional Imaging
- Visualization And Forensic Imaging
- PET/MRI
- Dual- and Multienergy CT
- Radiomics Research Group
- Prostate Research Group
- Bone marrow
- Musculoskeletal Imaging
- Microstructural Imaging Research Group
- Staff
- Patients
- Research
- Medical Physics in Radiology
- X-Ray Imaging and Computed Tomography
- Federated Information Systems
- Translational Molecular Imaging
- Medical Physics in Radiation Oncology
- Biomedical Physics in Radiation Oncology
- Intelligent Medical Systems
- Medical Image Computing
- Radiooncology - Radiobiology
- Smart Technologies for Tumor Therapy
- Radiation Oncology
- Molecular Radiooncology
- Nuclear Medicine
- Translational Radiation Oncology
- Translational Radiotheranostics
- Interactive Machine Learning
- Intelligent Systems and Robotics in Urology
- Multiparametric methods for early detection of prostate cancer
- Translational Molecular Imaging in Oncologic Therapy Monitoring
- Radiology
- Cell Biology and Tumor Biology
- Research Groups A-Z
- Junior Research Groups
- Core Facilities
- News
- List of Core Facilities
- Antibodies
- Cellular Tools
- Center for Preclinical Research
- Central Library
- Chemical Biology
- Dieter Morszeck Biorepository
- Electron Microscopy
- Flow Cytometry
- Information Technology ITCF
- Light Microscopy
- Metabolomics
- Microarray
- Microbiological Diagnostics
- Next Generation Sequencing
- Omics IT and Data Management
- Proteomics
- Radiopharmaceuticals and Preclinical Trials
- Single-cell Open Lab
- Small Animal Imaging
- Transgenic Service
- Tumor Models
- OMERO@DKFZ
- List of Technologies
- DKFZ Core Facilities Publication Policy
- Enabling Technology
- Data Science @ DKFZ
- INFORM
- Baden-Württemberg Cancer Registry
- Cooperations & Networks
- National Cooperations
- International Cooperations
- Cooperational Research Program with Israel: DKFZ - MOST in Cancer Research
- Program
- Members of the Program Committee
- Call
- Publication Database
- German-Israeli Cancer Research Schools
- Archive
- Heidelberg - Israel, Science and Culture
- Symposium 40 Years of German-Israeli Cooperation
- 35th Anniversary Symposium
- 34th Meeting of the DKFZ-MOST Program
- 40th Anniversary Publication
- 30th Anniversary Publication
- 20th Anniversary Publication
- Flyer - The Cancer Cooperation Program
- List Publications 1976-2004
- Highlight-Projects
- Cooperational Research Program with Israel: DKFZ - MOST in Cancer Research
- Cooperations with industrial companies
- DKFZ PostDoc Network
- Cross Program Topic RNA@DKFZ
- Cross Program Topic Epigenetics@dkfz
- Cross Program Topic Single Cell Sequencing
- WHO Collaborating Centers
- DKFZ Site Dresden
- Health + Life Science Alliance Heidelberg Mannheim
Unraveling the role of DDX RNA helicases in protein kinase regulation
![](/__we_thumbs__/91110_1_ddx.png)
Model for DDX proteins acting as nucleotide exchange factors for protein kinases. At high [S], binding of substrate may occur to CK2 in which ADP has not dissociated, leading to a [ADP-kinase-substrate] dead-end complex. DDX binding to protein kinase accelerates ADP release and reduces dead-end complex formation, thereby increasing reaction-rate.
© dkfz.de
DEAD-box (DDX) RNA helicases are a large family of ATPases, many of which have unknown functions. We previously identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt-β-catenin network in embryonic development, where it acts as a regulator of Casein kinase 1 epsilon (CK1e). DDX RNA helicases commonly promote RNA processing, but intriguingly, the DDX3X oncogene is as we showed also an activator of Casein kinase 1e (CK1e) in Wnt signaling.
We demonstrated that kinase stimulation is a latent property of many DDX proteins. Stimulation resides in the helicase core domain and engages RNA binding- but not catalytic motifs. In DDX3X, the C-terminus provides specificity for DVL2 condensates in Wnt/CK1esignaling. For Casein kinase 2 (CK2a2), we identified DDX1, -24, -41, and -54 as physiological activators. Mathematical modeling of enzyme kinetics and stopped-flow spectroscopy converge on the conclusion that DDX proteins function as nucleotide exchange factors to stimulate CK2a2 activity and overcome substrate inhibition. Our studies reveal protein kinase stimulation by nucleotide exchange as a new principle in kinase regulation and an evolved function of DDX proteins.
We conducted several large-scale screens to investigate if protein kinase-DDX interaction is a more widespread phenomenon. In these screens, we retrieved Ser/Thr protein kinases as prominent interactors of DDX/DHX proteins and found hundreds of binary interactions. We extracted members of eleven protein kinase families, which bind to- and are stimulated by DDX proteins, including CAMK, CDK, CK1, CK2, DYRK, MARK, NEK, PRKC, SRPK, STE7/MAP2K, and STE20/PAK family members. MARK1 was identified in all screens and enzyme kinetic validation confirmed DDX proteins as V-type activators of MARK1. The findings indicate pervasive interactions between protein kinases and DEAD box RNA helicases and they will provide a rich resource to explore their regulatory relationships.
Our working hypothesis is that the interaction between DDX proteins and protein kinases will be particularly important in phase separation where protein concentrations are very high. We therefore investigate the role of DDX3X in biomolecular condensates during Wnt signaling.
References
Cruciat CM, Dolde C, de Groot RE, Ohkawara B, Reinhard C, Korswagen HC, and Niehrs C. (2013). RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-β-catenin signaling. Science 339, 1436-1441.
Fatti E, Hirth A, Švorinić A, Günther M, Stier G, Cruciat CM, Acebrón SP, Papageorgiou D, Sinning I, Krijgsveld J, Höfer T, Niehrs C. (2023) DEAD box RNA helicases act as nucleotide exchange factors for casein kinase 2. Sci Signal. 25;
Hirth, A., Fatti, E., Netz, E., Acebron, S.P., Papageorgiou D., Švorinić, A., Cruciat, C.-M., Karaulanov, E., Gopanenko, A., Zhu, T., Sinning, I., Krijgsveld, J., Kohlbacher, O., Niehrs, C. (2024) DEAD box RNA helicases are pervasive protein kinase interactors and activators. Genome Res. doi: 10.1101/gr.278264.123.