Experimental and computational studies indicate specific binding of pVHL protein to Aurora-A kinase
Journal of Physical Chemistry B, ISSN: 1520-6106, Vol: 114, Issue: 3, Page: 1486-1497
2010
- 5Citations
- 12Captures
- 2Mentions
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Metrics Details
- Citations5
- Citation Indexes5
- CrossRef4
- Captures12
- Readers12
- 12
- Mentions2
- References2
- Wikipedia2
Article Description
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. © 2010 American Chemical Society.
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