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: Caroline F Mohr, Christine Gross, Matthias Bros, Angelika B Reske-Kunz, Brigitte Biesinger, Andrea K Thoma-Kress
• Journal: Virology (Virology) Vol. 485 Pg. 481-91 (Nov 2015) ISSN: 1096-0341 [Electronic] United States
• PMID: 26363219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• Gene Products, tax
• Microfilament Proteins
• NF-kappa B
• Protein Kinase Inhibitors
• fascin
• src-Family Kinases

Topics

• Carrier Proteins (genetics, metabolism)
• Cell Transformation, Viral
• Gene Expression Regulation (drug effects)
• Gene Products, tax (metabolism)
• Human T-lymphotropic virus 1 (genetics, metabolism)
• Humans
• Microfilament Proteins (genetics, metabolism)
• Models, Biological
• NF-kappa B (metabolism)
• Promoter Regions, Genetic
• Protein Kinase Inhibitors (pharmacology)
• Signal Transduction
• T-Lymphocytes (drug effects, metabolism, pathology, virology)
• Transcriptional Activation
• src-Family Kinases (antagonists & inhibitors, metabolism)