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Experimental and computational studies indicate specific binding of pVHL protein to Aurora-A kinase.

Abstract : Overexpression of Aurora-A kinase is commonly detected in many cancers, whereas the von Hippel-Lindau protein (pVHL) is frequently mutated or absent in renal cell carcinoma and is involved in the Ub proteasome complex, an important degradation pathway. In order to establish a link between Aurora-A overexpression and lack of pVHL protein, we hypothesized that pVHL regulates Aurora-A expression through a physical interaction. We present the first evidence, from both biological assays and computational biology techniques, that human pVHL binds strongly to Aurora-A kinase. Extensive molecular modeling, docking, and dynamic simulations demonstrate that the structure of the pVHL protein would allow it to bind to the TPX2 binding region of Aurora-A. In view of Aurora-A's importance as a therapeutic target for the treatment of cancer, this observation provides novel insights into the Aurora-A/pVHL pathway. In addition, the detailed Aurora-A/pVHL binding structure obtained will be valuable for the design of future Aurora-A inhibitors as therapeutic agents.
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https://www.hal.inserm.fr/inserm-00451872
Contributor : Hervé de Villemeur <>
Submitted on : Monday, February 1, 2010 - 9:36:42 AM
Last modification on : Wednesday, May 16, 2018 - 11:22:33 AM

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Imen Ferchichi, Nejla Stambouli, Raja Marrackchi, Yannick Arlot, Claude Prigent, et al.. Experimental and computational studies indicate specific binding of pVHL protein to Aurora-A kinase.. Journal of Physical Chemistry B, American Chemical Society, 2010, 114 (3), pp.1486-97. ⟨10.1021/jp909869g⟩. ⟨inserm-00451872⟩

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