6533b7d9fe1ef96bd126c483

RESEARCH PRODUCT

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.

Angelika B. Reske-kunzChristine GrossMatthias BrosAndrea K. Thoma-kressCaroline F. MohrBrigitte Biesinger

subject

Transcriptional ActivationT-LymphocytesTaxmacromolecular substancesBiologyModels BiologicalFascinDownregulation and upregulationVirologyTranscriptional regulationmedicineHumansPromoter Regions GeneticProtein Kinase InhibitorsOncogeneFascinRegulation of gene expressionHuman T-lymphotropic virus 1NF‐kappa B (NF‐KB)Microfilament ProteinsNF-kappa BPromoterTumor virusTranscription regulationGene Products taxmedicine.diseasebiology.organism_classificationCell Transformation ViralPP2DeltaretrovirusLeukemiasrc-Family KinasesGene Expression RegulationHTLV-1ATLHuman T-lymphotropic virus 1Cancer researchbiology.proteinSignal transductionCarrier ProteinsSignal Transduction

description

AbstractAdult 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.

yearjournalcountryeditionlanguage
2015-11-01Virology
10.1016/j.virol.2015.08.025https://pubmed.ncbi.nlm.nih.gov/26363219