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

Correspondence: Dr S Melmed, Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles, 8700 Beverly Blvd, Academic Affairs, Room 2015, Los-Angeles, CA 90048, USA. E-mail: melmed@csmc.edu

Received 1 April 2008; Revised 15 May 2008; Accepted 17 June 2008; Published online 28 July 2008.

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.