Upregulation of TPX2 by STAT3: identification of a novel STAT3 binding site.
TPX2, a protein involved in mitosis, is considered a good marker for actively proliferating tissues, highly expressed in a number of cancer cells. We show the presence of high-affinity binding site for STAT3 in the 5'-flanking region of the Tpx2 gene, which is in vivo bound by activated STAT3. A specific STAT3 peptide inhibitor represses the expression of the Tpx2 gene and inhibits the binding of STAT3 to its consensus sequence in human cell lines where STAT3 is activated. These results indicate that activated STAT3 contributes to the over-expression of Tpx2 through the binding to an enhancer site.
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, 00185 Roma, Italy.
Rossana
R
Cocchiola
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, 00185 Roma, Italy.
Caterina
C
Grillo
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, 00185 Roma, Italy.
Fabio
F
Altieri
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, 00185 Roma, Italy.
Silvia
S
Chichiarelli
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, 00185 Roma, Italy.
Carlo
C
Turano
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, 00185 Roma, Italy.
Margherita
M
Eufemi
D017209:Apoptosis; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C122167:TPX2 protein, human; D015534:Trans-Activators