title: Phosphorylation of TCTP as a marker for polo-like kinase-1 activity in vivo.
abstract: Polo-like kinase 1 (PLK1) is the master regulator of mitosis and a target for anticancer therapy. To develop a marker of PLK1 activity in cells and tumour tissues, this study focused on translational controlled tumour protein (TCTP) and identified serine 46 as a site phosphorylated by PLK1 in vitro. Using an antibody raised against phospho-TCTP-Ser46, it was demonstrated that phosphorylation at this site correlates with PLK1 level and kinase activity in cells. Moreover, PLK1 depletion by siRNA or inactivation by specific inhibitors caused a correspondent decrease in phospho-TCTP-Ser46 signal validating this site as a direct marker of PLK1. Using this marker, the study characterized PLK1 inhibitors in cells by setting up a high-content assay and finally immunohistochemical assay suitable for following inhibitor activity in preclinical tumour models and possibly in clinical studies was developed.
authors.affiliation: BU Oncology, Nerviano Medical Sciences srl, 20014 Nerviano, Italy.
authors.forename: Ulisse
authors.initials: U
authors.lastname: Cucchi
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gianellini
authors.forename: Anna
authors.initials: A
authors.lastname: De Ponti
authors.forename: Francesco
authors.initials: F
authors.lastname: Sola
authors.forename: Rachele
authors.initials: R
authors.lastname: Alzani
authors.forename: Veronica
authors.initials: V
authors.lastname: Patton
authors.forename: Alice
authors.initials: A
authors.lastname: Pezzoni
authors.forename: Sonia
authors.initials: S
authors.lastname: Troiani
authors.forename: Maria B
authors.initials: MB
authors.lastname: Saccardo
authors.forename: Simona
authors.initials: S
authors.lastname: Rizzi
authors.forename: Maria L
authors.initials: ML
authors.lastname: Giorgini
authors.forename: Paolo
authors.initials: P
authors.lastname: Cappella
authors.forename: Italo
authors.initials: I
authors.lastname: Beria
authors.forename: Barbara
authors.initials: B
authors.lastname: Valsasina
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000201:enzymology / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000201:enzymology / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D000090324:Tumor Protein, Translationally-Controlled 1; D000097869:Polo-Like Kinase 1
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000090324:Tumor Protein, Translationally-Controlled 1; D000097869:Polo-Like Kinase 1; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse