Pituitary tumor transforming gene 1 regulates Aurora kinase A activity.

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.

• Authors: Y Tong, A Ben-Shlomo, C Zhou, K Wawrowsky, S Melmed
• Journal: Oncogene (Oncogene) Vol. 27 Issue 49 Pg. 6385-95 (Oct 23 2008) ISSN: 1476-5594 [Electronic] England
• PMID: 18663361 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• Securin
• pituitary tumor-transforming protein 1, human
• AURKA protein, human
• Aurora Kinase A
• Aurora Kinases
• Protein Serine-Threonine Kinases

Topics

• Aurora Kinase A
• Aurora Kinases
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• Humans
• Neoplasm Proteins (genetics)
• Protein Serine-Threonine Kinases (analysis, genetics, metabolism)
• Securin
• Transfection