Aurora kinase

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Aurora kinases are serine/threonine kinases that are essential for cell proliferation. They are phosphotransferase enzymes that help the dividing cell dispense its genetic materials to its daughter cells. More specifically, Aurora kinases play a crucial role in cellular division by controlling chromatid segregation. Defects in this segregation can cause genetic instability, a condition which is highly associated with tumorigenesis.[1]

Three Aurora kinases have been identified in mammalian cells to date. Besides being implicated as mitotic regulators, these three kinases have generated significant interest in the cancer research field due to their elevated expression profiles in many human cancers.[2] The human Aurora kinases present a similar domain organization, with a N-terminal domain of 39–129 residues in length, a related Ser/Thr protein kinase domain and a short C-terminal domain containing 15–20 residues. The N-terminal domain of three proteins share low sequence conservation, which determines selectivity during protein–protein interactions.[1]


As described above, there are three classes of aurora kinases in multicellular organisms, including humans:

  • Aurora A (a.k.a. Aurora 2) functions during prophase of mitosis and is required for correct duplication and separation of the centrosomes (the microtubule organising centres in eukaryotic cells). Aurora A Activity is positively-regulated by the spindle protein TPX2,[3][4] and has recently been shown to be a target for thiol-containing molecules, such as Coenzyme A. [5]
  • Aurora B (a.k.a. Aurora 1) functions in the attachment of the mitotic spindle to the centromere.
  • Aurora C (AURKC) works in germ-line cells and little is known about its function.

Aurora kinase in Cancer[edit]

Aurora-A is a novel therapeutic target that belongs to the serine/threonine kinase family of proteins. The somatic mutation (S155R) in Aurora-A results in a loss of interaction with its binding partner TPX2. The S155R mutation thus leads to ectopic expression of Aurora-A, resulting in centrosome amplification, chromosomal instability, aneuploidy, and oncogenic transformations. Alantolactone and Dactylose-A were demonstrated as potential molecules that could bind to the interface pocket and restore the lost interaction between mutant Aurora-A and TPX2.[6]

Work strategy to identify potential modulators of Aurora-A and TPX2 complex [6]

See also[edit]


  1. ^ a b Bolanos-Garcia V M. Aurora kinases. The International Journal of Biochemistry & Cell Biology 37 (2005) 1572–1577.
  2. ^ Giet R, Prigent C. Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases. Journal of Cell Science 112 (1999) 3591–3601.
  3. ^ | vauthors = Eyers PA, Erikson E, Chen LG, Eyers PA | title = A novel mechanism for activation of the protein kinase Aurora A | journal = Current Biology | volume = 13 | issue = 8 | pages = 691–697 | date = April 2003 | pmid = 12699628 | doi = 10.1016/s0960-9822(03)00166-0 }}
  4. ^ | vauthors = Bayliss R, Sardon T, Vernos I, Conti E | title = Structural basis of Aurora-A activation by TPX2 at the mitotic spindle | journal = Molecular Cell | volume = 13 | issue = 8 | pages = 691–697 | date = April 2003 | pmid = 14580337| doi = 10.1016/s1097-2765(03)00392-7 }}
  5. ^ | vauthors = Tsuchiya Y, Byrne DP, Burgess SG, Bormann J, Bakovic J, Huang Y, Zhyvoloup A, Yu BY, Peak Chew S, Tran T, Bellany F, Tabor AB, Chan AE, Guruprasad L, Garifulin O, Filonenko V, Vonderach M, Ferries S, Eyers CE, Carroll J, Skehel M, Bayliss R, Eyers PA, Gout I | title = Covalent Aurora A regulation by the metabolic integrator coenzyme A | journal = Redox Biology | date = Sep 2019 | pmid = 31546169| doi = 10.1016/j.redox.2019.101318}}
  6. ^ a b Bhardwaj V, Purohit R (25 May 2020). "Targeting the protein-protein interface pocket of Aurora-A-TPX2 complex: rational drug design and validation". Journal of Biomolecular Structure and Dynamics. doi:10.1080/07391102.2020.1772109. PMID 32448055.

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