Specific Small-Molecule Activator of Aurora Kinase A Induces Autophosphorylation in a Cell-Free System

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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Abstract

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
Publication:	Journal of Medicinal Chemistry
Publisher:	American Chemical Society
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
URI:	http://eprints.iisc.ac.in/id/eprint/26711

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