Specific small-molecule activator of Aurora kinase A induces autophosphorylation in a cell-free system

Journal of Medicinal Chemistry
A Hari KishoreTapas K Kundu

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.

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Citations

Aug 11, 2010·Journal of Molecular Modeling·Ping LanWei-Min Chen
Jun 16, 2011·International Journal of Molecular Sciences·Yong AiFa-Jun Song
Jun 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Dhanasekaran KarthigeyanChandrabhas Narayana
Aug 21, 2014·Proceedings of the National Academy of Sciences of the United States of America·Anna S NikonovaErica A Golemis
Mar 10, 2010·Cellular and Molecular Life Sciences : CMLS·Maria Stasiuk, A Kozubek
Apr 22, 2015·International Journal of Molecular Sciences·Fatma B Hamad, Egid B Mubofu
Mar 3, 2010·Medicinal Research Reviews·Dhanasekaran KarthigeyanTapas K Kundu
May 2, 2018·Chemical & Pharmaceutical Bulletin·Muhammad Ajmal ShahPharkphoom Panichayupakaranant
Jul 28, 2017·Current Medicinal Chemistry·Resmi C PanickerRajavel Srinivasan
Jan 15, 2013·International Journal of Oncology·Yeong-Ae SeongGun-Do Kim
Nov 23, 2011·Basic & Clinical Pharmacology & Toxicology·Mahadevappa HemshekharKesturu S Girish
Oct 30, 2020·Protein Expression and Purification·May H Abdel AzizMichelle R Arkin
Oct 21, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Kelly WaltonBrian C Betts

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