title: Specific small-molecule activator of Aurora kinase A induces autophosphorylation in a cell-free system.
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.
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 06, India.
authors.forename: A Hari
authors.initials: AH
authors.lastname: Kishore
authors.forename: B M
authors.initials: BM
authors.lastname: Vedamurthy
authors.forename: K
authors.initials: K
authors.lastname: Mantelingu
authors.forename: Shipra
authors.initials: S
authors.lastname: Agrawal
authors.forename: B A Ashok
authors.initials: BA
authors.lastname: Reddy
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Roy
authors.forename: K S
authors.initials: KS
authors.lastname: Rangappa
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
mesh_terms: D048729:Anacardic Acids / Q000737:chemistry* / Q000302:isolation & purification; D031021:Anacardium; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002460:Cell Line; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D020536:Enzyme Activators / Q000737:chemistry* / Q000302:isolation & purification; D006657:Histones / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics; D013050:Spectrometry, Fluorescence
chemical_list: D048729:Anacardic Acids; D020536:Enzyme Activators; D006657:Histones; C088115:anacardic acid; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases