title: Regulation of the tumor marker Fascin by the viral oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) depends on promoter activation and on a promoter-independent mechanism.
abstract: Adult T-cell leukemia/lymphoma is a highly infiltrative neoplasia of CD4(+) T-lymphocytes that occurs in about 5% of carriers infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax perturbs cellular signaling pathways leading to upregulation of host cell factors, amongst them the actin-bundling protein Fascin, an invasion marker of several types of cancer. However, transcriptional regulation of Fascin by Tax is poorly understood. In this study, we identified a triple mode of transcriptional induction of Fascin by Tax, which requires (1) NF-κB-dependent promoter activation, (2) a Tax-responsive region in the Fascin promoter, and (3) a promoter-independent mechanism sensitive to the Src family kinase inhibitor PP2. Thus, Tax regulates Fascin by a multitude of signals. Beyond, using Tax-expressing and virus-transformed lymphocytes as a model system, our study is the first to identify the invasion marker Fascin as a novel target of PP2, an inhibitor of metastasis.
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. Electronic address: caroline.mohr@viro.med.uni-erlangen.de.
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Mohr
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. Electronic address: christine.gross@viro.med.uni-erlangen.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Gross
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany. Electronic address: mbros@uni-mainz.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bros
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany. Electronic address: A.Reske-Kunz@uni-mainz.de.
authors.forename: Angelika B
authors.initials: AB
authors.lastname: Reske-Kunz
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. Electronic address: Brigitte.Biesinger-Zwosta@viro.med.uni-erlangen.de.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Biesinger
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. Electronic address: aakress@viro.med.uni-erlangen.de.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Thoma-Kress
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002472:Cell Transformation, Viral; D005786:Gene Expression Regulation / Q000187:drug effects; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015533:Transcriptional Activation; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016356:Gene Products, tax; D008840:Microfilament Proteins; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C020324:fascin; D019061:src-Family Kinases
keywords: ATL; Fascin; HTLV-1; NF‐kappa B (NF‐KB); Oncogene; PP2; Promoter; Tax; Transcription regulation; Tumor virus