Pleiotropic Functions of HTLV-1 Tax Contribute to Cellular Transformation
نویسندگان
چکیده
Human T cell leukemia virus type-1 (HTLV-1) is the only retrovirus known to be the etiologic agent of a human cancer, adult T-cell leukemia/lymphoma (ATLL), a highly aggressive cancer of mature T cells. Epidemiological reports suggest that 10 to 20 million people throughout the world are infected with HTLV-1, which is endemic in parts of sub-Saharan Africa, the Caribbean, Japan, and South America [1]. HTLV-1 encodes a regulatory protein, Tax, which is essential for virus replication and plays a significant role in the oncogenic potential of HTLV-1. This chapter will summarize the effects of Tax on cellular processes including transcription, cell cycle checkpoints, and DNA repair, and will discuss how these activities may contribute to its transforming potential.
منابع مشابه
HTLV-I Tax-Mediated Inactivation of Cell Cycle Checkpoints and DNA Repair Pathways Contribute to Cellular Transformation: "A Random Mutagenesis Model".
To achieve cellular transformation, most oncogenic retroviruses use transduction by proto-oncogene capture or insertional mutagenesis, whereby provirus integration disrupts expression of tumor suppressors or proto-oncogenes. In contrast, the Human T-cell leukemia virus type 1 (HTLV-I) has been classified in a separate class referred to as "transactivating retroviruses". Current views suggest th...
متن کاملHuman T-cell leukemia virus type 2 tax mutants that selectively abrogate NFkappaB or CREB/ATF activation fail to transform primary human T cells.
Human T-cell leukemia virus (HTLV) Tax protein has been implicated in the HTLV oncogenic process, primarily due to its pleiotropic effects on cellular genes involved in growth regulation and cell cycle control. To date, several approaches attempting to correlate Tax activation of the CREB/activating transcription factor (ATF) or NFkappaB/Rel transcriptional activation pathway to cellular transf...
متن کاملTranscriptional Activity of HTLV-I Tax Influences the Expression of Marker Genes Associated with Cellular Transformation
Human T cell leukemia virus type I (HTLV-I) has been identified as the etiologic agent of adult T cell leukemia (ATL). HTLV-I encodes a transcriptional regulatory protein, Tax, which also functions as the viral transforming protein. Through interactions with a number of cellular transcription factors Tax can modulate cellular gene expression. Since the majority of Tax-responsive cellular genes ...
متن کاملSetting the stage for transformation: HTLV-1 Tax inhibition of p53 function.
Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Although the precise mechanism of HTLV-1 oncogenesis remains unclear, the pathogenesis has been linked to the pleiotropic activity of the viral transcriptional activator protein Tax. Tax has been shown to regulate viral and cellular ...
متن کاملHTLV Tax: A Fascinating Multifunctional Co-Regulator of Viral and Cellular Pathways
Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2-5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, incl...
متن کامل