Pituitary tumor transforming gene 1 regulates Aurora kinase A activity.
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.
Tong
Y
Y
Department of Medicine, Cedars-Sinai Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USA.
Ben-Shlomo
A
A
Zhou
C
C
Wawrowsky
K
K
Melmed
S
S
D064096:Aurora Kinase A; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D014162:Transfection
D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases