4.8 Review

The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target

Related references

Note: Only part of the references are listed.
Article Medicine, Research & Experimental

DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3

Rahul S. Bhansali et al.

Summary: The study reveals that DYRK1A is overexpressed in and essential for B-ALL, with FOXO1 and STAT3 being critical substrates. Loss of DYRK1A-mediated FOXO1 and STAT3 signaling disrupts DNA damage and ROS regulation, leading to preferential cell death in leukemic B cells.

JOURNAL OF CLINICAL INVESTIGATION (2021)

Article Biochemistry & Molecular Biology

DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

Brianna Chen et al.

Summary: The study demonstrates the important role of DYRK1A kinase in regulating the differentiation commitment of glioblastoma stem cells. Inhibiting DYRK1A insulates GSCs from differentiation-inducing signals, promoting differentiation and limiting stemness acquisition through deactivation of CDK5. This novel DYRK1A-CDK5-SOX2 pathway sheds further light on the mechanisms underlying the maintenance of glioblastoma stem cells.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Chemistry, Medicinal

Structure-Guided Discovery of Potent and Selective DYRK1A Inhibitors

Csaba Weber et al.

Summary: The kinase DYRK1A has been identified as a promising target for drug discovery, and a biaryl compound was developed through fragment screening to efficiently bind to its ATP site. Structural optimization cycles resulted in the transformation of this compound into potent and selective DYRK1A inhibitors, with a focus on fine-tuning selectivity by exploiting structural differences with DYRK2. These inhibitors demonstrated potent inhibition of DYRK1A in cell culture and in vivo, with drug-like properties and dose-dependent tumor growth inhibition in an ovarian carcinoma model.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Cell Biology

Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells

Ariadna Recasens et al.

Summary: DYRK1A has been reported to have both tumour suppressive and oncogenic functions. In glioblastoma, its role depends on RB expression and the level of DYRK1A activity. Moderate DYRK1A inhibition increases proliferation, while complete inhibition leads to cell cycle arrest regardless of RB status.

CELL DEATH DISCOVERY (2021)

Article Hematology

DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and B-cell leukemogenesis

Yanchuan Li et al.

Summary: DYRK1a is identified as a critical mediator in the BAFF signaling pathway, playing a key role in B-cell survival and contributing to the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL).

BLOOD (2021)

Article Oncology

DYRK1A is required for maintenance of cancer stemness, contributing to tumorigenic potential in oral/oropharyngeal squamous cell carcinoma

Charlotte Ellen Martin et al.

Summary: DYRK1A plays a crucial role in maintaining tumor growth and stemness in oral/oropharyngeal squamous cell carcinoma cells. Deletion of DYRK1A suppresses cancer stem-like cell properties, while ectopic expression enhances the CSC phenotype. Additionally, DYRK1A's regulation of CSCs in OSCC is mediated through the FGF2 pathway.

EXPERIMENTAL CELL RESEARCH (2021)

Article Cell Biology

DYRK1A phosphorylates MEF2D and decreases its transcriptional activity

Pin Wang et al.

Summary: Dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) was found to phosphorylate MEF2D at Ser251, leading to increased MEF2D protein level but decreased transcriptional activity, which in turn resulted in reduced expression of MEF2D target genes. This interaction between DYRK1A and MEF2D may play a role in regulating gene expression.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2021)

Article Chemistry, Medicinal

Fragment-Derived Selective Inhibitors of Dual-Specificity Kinases DYRK1A and DYRK1B

David Lee Walmsley et al.

Summary: The serine/threonine kinase DYRK1A is associated with cancer progression and severity of symptoms in Down's syndrome. A highly selective and well-tolerated DYRK1A inhibitor has been identified, showing in vivo activity in a tumor model, and providing a useful tool for further research on the effects of DYRK1A inhibition in disease models.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors

Scott H. Henderson et al.

Summary: DYRK1A plays a crucial role in regulating the proliferation and differentiation of neuronal progenitor cells, making it a potential target for the treatment of neurodegenerative diseases and diabetes. The development of pyrazolo[1,5-b]pyridazin inhibitors with good physicochemical properties and selectivity over the kinome has opened up new possibilities for the discovery of therapies targeting DYRK1A function. Compound 11 demonstrated promising permeability and cellular activity, positioning it as a potential candidate for in vivo studies.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Cell Biology

K63-linked ubiquitination of DYRK1A by TRAF2 alleviates Sprouty 2-mediated degradation of EGFR

Pengshan Zhang et al.

Summary: DYRK1A plays a role in multiple cellular pathways and interacts with TRAF2 to translocate to vesicle membranes, affecting the degradation of EGFR. This axis could be a potential target for new therapeutic developments.

CELL DEATH & DISEASE (2021)

Review Biochemistry & Molecular Biology

Alternative splicing and cancer: a systematic review

Yuanjiao Zhang et al.

Summary: The study systematically describes the abnormal regulation and functions of alternative splicing in tumors, as well as introduces therapeutic strategies targeting splicing catalysis and regulatory proteins. Further research is needed to fully understand the association between alternative splicing and cancer.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

Article Biochemistry & Molecular Biology

Licocoumarone induces BxPC-3 pancreatic adenocarcinoma cell death by inhibiting DYRK1A

Chao Zhao et al.

CHEMICO-BIOLOGICAL INTERACTIONS (2020)

Review Oncology

FOXO transcription factor family in cancer and metastasis

Yannasittha Jiramongkol et al.

CANCER AND METASTASIS REVIEWS (2020)

Article Biochemistry & Molecular Biology

Small Molecule Inhibitors of DYRK1A Identified by Computational and Experimental Approaches

Hye Ree Yoon et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Review Chemistry, Medicinal

Pharmacological effects of harmine and its derivatives: a review

Liang Zhang et al.

ARCHIVES OF PHARMACAL RESEARCH (2020)

Article Multidisciplinary Sciences

The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair

Steven E. Guard et al.

SCIENTIFIC REPORTS (2019)

Article Multidisciplinary Sciences

A comprehensive proteomics-based interaction screen that links DYRK1A to RNF169 and to the DNA damage response

Julia Roewenstrunk et al.

SCIENTIFIC REPORTS (2019)

Article Cell Biology

DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild-type NSCLC cells to AZD9291

Yang-ling Li et al.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2019)

Article Gastroenterology & Hepatology

DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth

Jeroni Luna et al.

Article Multidisciplinary Sciences

Visualization and quantification of dynamic STAT3 homodimerization in living cells using homoFluoppi

Yusuke Okada et al.

SCIENTIFIC REPORTS (2018)

Article Cell Biology

DYRK1A Kinase Positively Regulates Angiogenic Responses in Endothelial Cells

Esteban J. Rozen et al.

CELL REPORTS (2018)

Review Oncology

MuvB: A Key to Cell Cycle Control in Ovarian Cancer

Audra N. Iness et al.

FRONTIERS IN ONCOLOGY (2018)

Article Multidisciplinary Sciences

Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II

Huasong Lu et al.

NATURE (2018)

Article Multidisciplinary Sciences

DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B

Mina Yousefelahiyeh et al.

PLOS ONE (2018)

Article Oncology

NOTCH3 expression is linked to breast cancer seeding and distant metastasis

Alexey A. Leontovich et al.

BREAST CANCER RESEARCH (2018)

Review Oncology

Ubiquitin ligases in oncogenic transformation and cancer therapy

Daniela Senft et al.

NATURE REVIEWS CANCER (2018)

Review Biochemistry & Molecular Biology

Cancer stem cells revisited

Eduard Batlle et al.

NATURE MEDICINE (2017)

Article Biochemistry & Molecular Biology

E3 Ligase SCFβTrCP-induced DYRK1A Protein Degradation Is Essential for Cell Cycle Progression in HEK293 Cells

Qiang Liu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2016)

Article Multidisciplinary Sciences

An ID2-dependent mechanism for VHL inactivation in cancer

Sang Bae Lee et al.

NATURE (2016)

Article Multidisciplinary Sciences

A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

Aneesha Radhakrishnan et al.

SCIENTIFIC REPORTS (2016)

Review Clinical Neurology

Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson's Disease?

Atbin Djamshidian et al.

MOVEMENT DISORDERS CLINICAL PRACTICE (2016)

Article Biochemistry & Molecular Biology

DYRK1A overexpression enhances STAT activity and astrogliogenesis in a Down syndrome mouse model

Nobuhiro Kurabayashi et al.

EMBO REPORTS (2015)

Article Biochemistry & Molecular Biology

Chromatin-wide Profiling of DYRK1A Reveals a Role as a Gene-Specific RNA Polymerase II CTD Kinase

Chiara Di Vona et al.

MOLECULAR CELL (2015)

Article Multidisciplinary Sciences

Proinflammatory TLR signalling is regulated by a TRAF2-dependent proteolysis mechanism in macrophages

Jin Jin et al.

NATURE COMMUNICATIONS (2015)

Review Biochemistry & Molecular Biology

Alkaloids from Marine Invertebrates as Important Leads for Anticancer Drugs Discovery and Development

Concetta Imperatore et al.

MOLECULES (2014)

Article Multidisciplinary Sciences

Requirement of MEF2A, C, and D for skeletal muscle regeneration

Ning Liu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Article Medicine, Research & Experimental

Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth

Natividad Pozo et al.

JOURNAL OF CLINICAL INVESTIGATION (2013)

Article Biochemistry & Molecular Biology

Structures of Down Syndrome Kinases, DYRKs, Reveal Mechanisms of Kinase Activation and Substrate Recognition

Meera Soundararajan et al.

STRUCTURE (2013)

Review Cell Biology

REST: an oncogene or a tumor suppressor?

Sara Negrini et al.

TRENDS IN CELL BIOLOGY (2013)

Article Medicine, Research & Experimental

Increased dosage of the chromosome 21 ortholog Dyrk1a promotes megakaryoblastic leukemia in a murine model of Down syndrome

Sebastien Malinge et al.

JOURNAL OF CLINICAL INVESTIGATION (2012)

Article Dermatology

Role and Regulation of STAT3 Phosphorylation at Ser727 in Melanocytes and Melanoma Cells

Masanobu Sakaguchi et al.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2012)

Article Geriatrics & Gerontology

Regulation of alternative splicing of tau exon 10 by 9G8 and Dyrk1A

Shaohong Ding et al.

NEUROBIOLOGY OF AGING (2012)

Article Cell & Tissue Engineering

REST Regulates Oncogenic Properties of Glioblastoma Stem Cells

Mohamed M. Kamal et al.

STEM CELLS (2012)

Article Biochemistry & Molecular Biology

DYRK1A binds to an evolutionarily conserved WD40-repeat protein WDR68 and induces its nuclear translocation

Yoshihiko Miyata et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2011)

Article Cell Biology

DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly

Larisa Litovchick et al.

GENES & DEVELOPMENT (2011)

Article Biochemistry & Molecular Biology

Splice Variants of the Dual Specificity Tyrosine Phosphorylation-regulated Kinase 4 (DYRK4) Differ in Their Subcellular Localization and Catalytic Activity

Chrisovalantis Papadopoulos et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2011)

Article Biochemistry & Molecular Biology

REST Regulates DYRK1A Transcription in a Negative Feedback Loop

Mei Lu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2011)

Article Clinical Neurology

Link Between DYRK1A Overexpression and Several-Fold Enhancement of Neurofibrillary Degeneration With 3-Repeat Tau Protein in Down Syndrome

Jerzy Wegiel et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2011)

Article Biochemistry & Molecular Biology

FGF-2 Regulates Cell Proliferation, Migration, and Angiogenesis through an NDY1/KDM2B-miR-101-EZH2 Pathway

Filippos Kottakis et al.

MOLECULAR CELL (2011)

Review Biochemistry & Molecular Biology

STAT3 SIGNALING: Anticancer Strategies and Challenges

Paul A. Johnston et al.

MOLECULAR INTERVENTIONS (2011)

Article Biochemistry & Molecular Biology

Regulation of the alternative splicing of tau exon 10 by SC35 and Dyrk1A

Wei Qian et al.

NUCLEIC ACIDS RESEARCH (2011)

Review Biochemistry & Molecular Biology

Natural Polyphenols that Display Anticancer Properties through Inhibition of Kinase Activity

D. Lamoral-Theys et al.

CURRENT MEDICINAL CHEMISTRY (2010)

Article Biochemistry & Molecular Biology

ATM Augments Nuclear Stabilization of DYRK2 by Inhibiting MDM2 in the Apoptotic Response to DNA Damage

Naoe Taira et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

Article Biochemistry & Molecular Biology

DYRK1A and DYRK3 Promote Cell Survival through Phosphorylation and Activation of SIRT1

Xiumei Guo et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

Article Biochemistry & Molecular Biology

Dyrk1A Phosphorylates p53 and Inhibits Proliferation of Embryonic Neuronal Cells

Joongkyu Park et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

Article Biochemistry & Molecular Biology

Characterization of a Domain that Transiently Converts Class 2 DYRKs into Intramolecular Tyrosine Kinases

Ross Kinstrie et al.

SCIENCE SIGNALING (2010)

Article Genetics & Heredity

DYRK1A-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome

Claudia Canzonetta et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2008)

Review Chemistry, Multidisciplinary

Lamellarins and related pyrrole-derived alkaloids from marine organisms

Hui Fan et al.

CHEMICAL REVIEWS (2008)

Article Biochemistry & Molecular Biology

Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome

Jianhua Shi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2008)

Article Multidisciplinary Sciences

SCFβ-TRCP controls oncogenic transformation and neural differentiation through REST degradation

Thomas F. Westbrook et al.

NATURE (2008)

Article Multidisciplinary Sciences

NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21

Joseph R. Arron et al.

NATURE (2006)

Article Biochemistry & Molecular Biology

Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions

Weihong Yin et al.

MOLECULAR CANCER (2006)

Review Immunology

NFAT proteins: Key regulators of T-cell development and function

F Macian

NATURE REVIEWS IMMUNOLOGY (2005)

Article Biochemistry & Molecular Biology

FOXO forkhead transcription factors induce G2-M checkpoint in response to oxidative stress

Y Furukawa-Hibi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2002)

Article Cell Biology

The role of NFAT transcription factors in integrin-mediated carcinoma invasion

S Jauliac et al.

NATURE CELL BIOLOGY (2002)