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BmB Reports

Regulation of CMGC kinases by hypoxia

  • 작성자

    Sang Bae Lee
  • 작성일자

    2023-12-21
  • 조회수

    602
Name: Sang Bae Lee ( leesb@jbnu.ac.kr )
2023-presentAssociate Professor, Division of Life Sciences, Jeonbuk National University
2019-2023Assistant Professor, Division of Life Sciences, Jeonbuk National University
2017-2019Associate Research Scientist, Institute for Cancer Genetics, Columbia University, New York, USA
2013-2017Postdoctoral Research Scientist, Institute for Cancer Genetics, Columbia University, New York, USA
2011-2012Postdoctoral research fellow, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine
2006-2011Ph.D., Sungkyunkwan University

Regulation of CMGC kinases by hypoxia

Hypoxia, a widespread occurrence observed in various malignant tumors, results from rapid tumor growth that outpaces the oxygen supply. Tumor hypoxia precipitates several effects on tumor biology; these include activating angiogenesis, intensifying invasiveness, enhancing the survival of tumor cells, suppressing anti-tumor immunity, and fostering resistance to therapy. Aligned with the findings that correlate CMGC kinases with the regulation of Hypoxia-Inducible Factor (HIF), a pivotal modulator, reports also indicate that hypoxia governs the activity of CMGC kinases, including DYRK1 kinases. Prolyl hydroxylation of DYRK1 kinases by PHD1 constitutes a novel mechanism of kinase maturation and activation. This modification "primes" DYRK1 kinases for subsequent tyrosine autophosphorylation, a vital step in their activation cascade. This mechanism adds a layer of intricacy to comprehending the regulation of CMGC kinases, and underscores the complex interplay between distinct post-translational modifications in harmonizing precise kinase activity. Overall, hypoxia assumes a substantial role in cancer progression, influencing diverse aspects of tumor biology that include angiogenesis, invasiveness, cell survival, and resistance to treatment. CMGC kinases are deeply entwined in its regulation. To fathom the molecular mechanisms underpinning hypoxia's impact on cancer cells, comprehending how hypoxia and prolyl hydroxylation govern the activity of CMGC kinases, including DYRK1 kinases, becomes imperative. This insight may pave the way for pioneering therapeutic approaches that target the hypoxic tumor microenvironment and its associated challenges.


BMB Rep. 2023 Nov;56(11):584-593. doi: 10.5483/BMBRep.2023-0165.
https://pubmed.ncbi.nlm.nih.gov/37915135/