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Molecular and Cellular Biology, July 2005, p. 5789-5800, Vol. 25, No. 14
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.14.5789-5800.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Phosphorylation and Stabilization of HURP by Aurora-A: Implication of HURP as a Transforming Target of Aurora-A

Chang-Tze Ricky Yu,1 Jung-Mao Hsu,1 Yuan-Chii Gladys Lee,1,2 Ann-Ping Tsou,3 Chen-Kung Chou,1,4 and Chi-Ying F. Huang1,3,5*

Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County 350,1 Graduate Institute of Medical Informatics, Taipei Medical University, Taipei 110,2 Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 112,3 Department of Life Science, Chang Gung University, Tao-Yuan 333,4 Department of Computer Science and Information Engineering, National Taiwan University, Taipei 106, Taiwan, Republic of China5

Received 18 January 2005/ Returned for modification 16 February 2005/ Accepted 11 April 2005

Aurora-A, a mitotic serine/threonine kinase with oncogene characteristics, has recently drawn intense attention because of its association with the development of human cancers and its relationship with mitotic progression. Using the gene expression profiles of Aurora-A as a template to search for and compare transcriptome expression profiles in publicly accessible microarray data sets, we identified HURP (encodes hepatoma upregulated protein) as one of the best Aurora-A-correlated genes. Empirical validation indicates that HURP has several characteristics in common with Aurora-A. These two genes have similar expression patterns in hepatocellular carcinoma, liver regeneration after partial hepatectomy, and cell cycle progression and across a variety of tissues and cell lines. Moreover, Aurora-A phosphorylated HURP in vitro and in vivo. Ectopic expression of either the catalytically inactive form of Aurora-A or the HURP-4P mutant, in which the Aurora-A phosphorylation sites were replaced with Ala, resulted in HURP instability and complex disassembly. In addition, HURP-wild-type stable transfectants were capable of growing in low-serum environments whereas HURP-4P grew poorly under low-serum conditions and failed to proliferate. These studies together support the view that the ability to integrate evidence derived from microarray studies into biochemical analyses may ultimately augment our predictive power when analyzing the potential role of poorly characterized proteins. While this combined approach was simply an initial attempt to answer a range of complex biological questions, our findings do suggest that HURP is a potential oncogenic target of Aurora-A.


* Corresponding author. Mailing address: National Health Research Institutes, Division of Molecular and Genomic Medicine, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China. Phone: (886) 37-246-166, ext. 35305 or 35306. Fax: (886) 37-586-459. E-mail: chiying{at}nhri.org.tw.


Molecular and Cellular Biology, July 2005, p. 5789-5800, Vol. 25, No. 14
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.14.5789-5800.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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