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

Journal

ONCOGENE
Volume 41, Issue 14, Pages 2003-2011

Publisher

SPRINGERNATURE
DOI: 10.1038/s41388-022-02245-6

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Funding

  1. NIH [R35 CA253096]
  2. St. Jude/ALSAC
  3. American Society of Hematology's Medical Student PhysicianScientist Award

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DYRK1A is an important enzyme that plays a crucial role not only in Down syndrome and neurodegenerative diseases, but also in cancer by regulating various biological processes. It acts as both an oncogene and a tumor suppressor depending on the cellular context.
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.

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