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Pituitary tumor transforming gene 1 regulates Aurora kinase A activity

Oncogene volume 27, pages 6385–6395 (2008)Cite this article

Abstract

Pituitary tumor transforming gene 1 (PTTG1), a transforming gene highly expressed in several cancers, is a mammalian securin protein regulating both G1/S and G2/M phases. Using protein array screening, we showed PTTG1 interacting with Aurora kinase A (Aurora-A), and confirmed the interaction using co-immunoprecipitation, His-tagged pull-down assays and intracellular immunofluorescence colocalization. PTTG1 transfection into HCT116 cells prevented Aurora-A T288 autophosphorylation, inhibited phosphorylation of the histone H3 Aurora-A substrate and resulted in abnormally condensed chromatin. PTTG1-null cell proliferation was more sensitive to Aurora-A knock down and to Aurora kinase Inhibitor III treatment. The results indicate that PTTG1 and Aurora-A interact to regulate cellular responses to anti-neoplastic drugs. PTTG1 knockdown is therefore a potential approach to improve the efficacy of tumor Aurora kinase inhibitors.

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Abbreviations

Aurora-A:

Aurora kinase A

PTTG1:

pituitary tumor transforming gene 1

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Acknowledgements

PTTG1 WT and KO HCT116 cells were kindly provided by Dr Bert Vogelstein, Johns Hopkins University. PTTG1-GFP and PTTG1-PCDNA3.1 plasmids were kindly provided by Dr Run Yu. Supported by NIH Grant CA 75979 (SM), T32 DK007770, and The Doris Factor Molecular Endocrinology Laboratory.

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  1. Department of Medicine, Cedars-Sinai Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Y Tong, A Ben-Shlomo, C Zhou, K Wawrowsky & S Melmed

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  1. Y Tong
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Correspondence to S Melmed.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Tong, Y., Ben-Shlomo, A., Zhou, C. et al. Pituitary tumor transforming gene 1 regulates Aurora kinase A activity. Oncogene 27, 6385–6395 (2008). https://doi.org/10.1038/onc.2008.234

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