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Review
. 2015 Jan 30;2(1):e970048.
doi: 10.4161/23723548.2014.970048. eCollection 2015 Jan-Mar.

DYRK1A: the double-edged kinase as a protagonist in cell growth and tumorigenesis

P Fernández-Martínez  1 , C Zahonero  2 , P Sánchez-Gómez  2
Affiliations
Review

DYRK1A: the double-edged kinase as a protagonist in cell growth and tumorigenesis

P Fernández-Martínez et al. Mol Cell Oncol. .

Abstract

DYRK1A (dual-specificity tyrosine-regulated kinase 1A) is a kinase with multiple implications for embryonic development, especially in the nervous system where it regulates the balance between proliferation and differentiation of neural progenitors. The DYRK1A gene is located in the Down syndrome critical region and may play a significant role in the developmental brain defects, early neurodegeneration, and cancer susceptibility of individuals with this syndrome. DYRK1A is also expressed in adults, where it might participate in the regulation of cell cycle, survival, and tumorigenesis, thus representing a potential therapeutic target for certain types of cancer. However, the final readout of DYRK1A overexpression or inhibition depends strongly on the cellular context, as it has both tumor suppressor and oncogenic activities. Here, we will discuss the functions and substrates of DYRK1A associated with the control of cell growth and tumorigenesis with a focus on the potential use of DYRK1A inhibitors in cancer therapy.

Keywords: DYRK1A; cancer; cell differentiation; cell proliferation; neural progenitors.

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Figures

Figure 1.
Figure 1.
DYRK1A activity blocks cell cycle progression. DYRK1A is considered primarily an inhibitor of proliferation due to its capacity to either block (red lines) cell cycle promoters (green boxes), or activate (green arrows) cell cycle inhibitors (red boxes).
Figure 2.
Figure 2.
Double-edged regulation of tumorigenesis by DYRK1A. DYRK1A has been associated with protumoral activity (green boxes) by activating (green arrows) known oncogenic proteins (red boxes) or by inhibiting (red lines) tumor suppressors (red boxes). However, an antitumoral capacity of DYRK1A has been also described through its activation of tumor suppressors or its inhibition of oncogenic proteins. To add complexity to DYRK1A function, some of the known substrates of this kinase can have both oncogenic and tumor suppressor activities (green and red boxes), depending on the cellular context and the developmental stage.
See this image and copyright information in PMC

References

    1. Becker W, Joost HG. Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity. Prog Nucleic Acid Res Mol Biol 1999; 62:1-17; PMID:9932450; http://dx.doi.org/ 10.1016/S0079-6603(08)60503-6 - DOI - PubMed
    1. Aranda S, Laguna A, de la LS. DYRK family of protein kinases: evolutionary relationships, biochemical properties, and functional roles. FASEB J 2011; 25(2):449-62; PMID:21048044; http://dx.doi.org/ 10.1096/fj.10-165837 - DOI - PubMed
    1. Kentrup H, Becker W, Heukelbach J, Wilmes A, Schurmann A, Huppertz C, Kainulainen H, Joost HG. Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII. J Biol Chem 1996; 271(7):3488-95; PMID:8631952; http://dx.doi.org/ 10.1074/jbc.271.7.3488 - DOI - PubMed
    1. Himpel S, Panzer P, Eirmbter K, Czajkowska H, Sayed M, Packman LC, Blundell T, Kentrup H, Grötzinger J, Joost HG, et al. Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A. Biochem J 2001; 359(Pt 3):497-505; PMID:11672423; http://dx.doi.org/ 10.1042/0264-6021:3590497 - DOI - PMC - PubMed
    1. Lochhead PA, Sibbet G, Morrice N, Cleghon V. Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell 2005; 121(6):925-36; PMID:15960979; http://dx.doi.org/ 10.1016/j.cell.2005.03.034 - DOI - PubMed