Kishore, A Hari and Vedamurthy, BM and Mantelingu, K and Agrawal, Shipra and Reddy, BA Ashok and Roy, Siddhartha and Rangappa, KS and Kundu, Tapas K (2008) Specific Small-Molecule Activator of Aurora Kinase A Induces Autophosphorylation in a Cell-Free System. In: Journal of Medicinal Chemistry, 51 (4). 792-797.
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Aurora kinases are essential for chromosomal segregation and cell division and thereby important for maintaining the proper genomic integrity. There are three classes of aurora kinases in humans: A, B, and C. Aurora kinase A is frequently overexpressed in various cancers. The link of the overexpression and tumorigenesis is yet to be understood. By employing virtual screening, we have found that anacardic acid, a pentadecane aliphatic chain containing hydroxylcarboxylic acid, from cashew nut shell liquid could be docked in Aurora kinases A and B. Remarkably, we found that anacardic acid could potently activate the Aurora kinase A mediated phosphorylation of histone H3, but at a similar concentration the activity of aurora kinase B remained unaffected in vitro. Mechanistically, anacardic acid induces the structural changes and also the autophosphorylation of the aurora kinase A to enhance the enzyme activity. This data thus indicate anacardic acid as the first small-molecule activator of Aurora kinase, which could be highly useful for probing the function of hyperactive (overexpressed) Aurora kinase A.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to American Chemical Society.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||04 Jun 2010 07:18|
|Last Modified:||19 Sep 2010 05:58|
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