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- Title
Pituitary tumor transforming gene 1 regulates Aurora kinase A activity.
- Authors
Tong, Y; Ben-Shlomo, A; Zhou, C; Wawrowsky, K; Melmed, S
- 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.
- Publication
Oncogene, 2008, Vol 27, Issue 49, p6385
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/onc.2008.234