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

Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) is a serine/threonine kinase that belongs to the DYRK family of proteins, a subgroup of the evolutionarily conserved CMGC protein kinase superfamily. Due to its localization on chromosome 21, the biological significance of DYRK1...

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Bibliographic Details
Published in:Oncogene 2022-04, Vol.41 (14), p.2003-2011
Main Authors: Rammohan, Malini, Harris, Ethan, Bhansali, Rahul S., Zhao, Emily, Li, Loretta S., Crispino, John D.
Format: Article
Language:English
Subjects:
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Apoptosis
Cancer
Cell Biology
Cell cycle
Chromosome 21
Chromosomes, Human, Pair 21 - metabolism
DNA damage
DNA repair
Down's syndrome
Dyrk Kinases
Human Genetics
Humans
Internal Medicine
Kinases
Localization
Medicine
Medicine & Public Health
Neoplasms - genetics
Neurodegenerative diseases
Oncogenes
Oncology
Phosphorylation
Protein Serine-Threonine Kinases - genetics
Protein-serine/threonine kinase
Protein-tyrosine kinase
Protein-Tyrosine Kinases - genetics
Review Article
Stem cells
Therapeutic applications
Therapeutic targets
Transcription
Tumor suppressor genes
Tumors
Ubiquitination
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Summary:Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) is a serine/threonine kinase that belongs to the DYRK family of proteins, a subgroup of the evolutionarily conserved CMGC protein kinase superfamily. Due to its localization on chromosome 21, the biological significance of DYRK1A was initially characterized in the pathogenesis of Down syndrome (DS) and related neurodegenerative diseases. However, increasing evidence has demonstrated a prominent role in cancer through its ability to regulate biologic processes including cell cycle progression, DNA damage repair, transcription, ubiquitination, tyrosine kinase activity, and cancer stem cell maintenance. DYRK1A has been identified as both an oncogene and tumor suppressor in different models, underscoring the importance of cellular context in its function. Here, we review mechanistic contributions of DYRK1A to cancer biology and its role as a potential therapeutic target.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-022-02245-6