title: TAF4b and Jun/activating protein-1 collaborate to regulate the expression of integrin alpha6 and cancer cell migration properties.
abstract: The TAF4b subunit of the transcription factor IID, which has a central role in transcription by polymerase II, is involved in promoter recognition by selective recruitment of activators. The activating protein-1 (AP-1) family members participate in oncogenic transformation via gene regulation. Utilizing immunoprecipitation of endogenous protein complexes, we documented specific interactions between Jun family members and TATA box binding protein-associated factors (TAF) in colon HT29 adenocarcinoma cells. Particularly, TAF4b and c-Jun were found to colocalize and interact in the nucleus of advanced carcinoma cells and in cells with epithelial-to-mesenchymal transition (EMT) characteristics. TAF4b was found to specifically regulate the AP-1 target gene involved in EMT integrin alpha6, thus altering related cellular properties such as migration potential. Using a chromatin immunoprecipitation approach in colon adenocarcinoma cell lines, we further identified a synergistic role for TAF4b and c-Jun and other AP-1 family members on the promoter of integrin alpha6, underlining the existence of a specific mechanism related to gene expression control. We show evidence for the first time of an interdependence of TAF4b and AP-1 family members in cell type-specific promoter recognition and initiation of transcription in the context of cancer progression and EMT.
authors.affiliation: Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
authors.forename: Margarita
authors.initials: M
authors.lastname: Kalogeropoulou
authors.forename: Angeliki
authors.initials: A
authors.lastname: Voulgari
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kostourou
authors.forename: Raphael
authors.initials: R
authors.lastname: Sandaltzopoulos
authors.forename: Rivka
authors.initials: R
authors.lastname: Dikstein
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tora
authors.forename: Alexander
authors.initials: A
authors.lastname: Pintzas
mesh_terms: D018938:Caco-2 Cells; D054337:Cell Dedifferentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D039503:Integrin alpha6; C101881:TAF4B protein, human; D035381:TATA-Binding Protein Associated Factors; D018808:Transcription Factor AP-1; D035362:Transcription Factor TFIID