The HTLV-1 Tax interactome

Abstract

The Tax1 oncoprotein encoded by Human T-lymphotropic virus type I is a major determinant of viral persistence and pathogenesis. Tax1 affects a wide variety of cellular signalling pathways leading to transcriptional activation, proliferation and ultimately transformation. To carry out these functions, Tax1 interacts with and modulates activity of a number of cellular proteins. In this review, we summarize the present knowledge of the Tax1 interactome and propose a rationale for the broad range of cellular proteins identified so far.

Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

“…Previous study has demonstrated that Tax protein may interact with some transcription factors and/or other transcriptional regulators and influence gene expression (Boxus et al, 2008). To elucidate whether Tax inflences HMGB1 expression in the CD4 + T-cells, in the current study, we directly extracted total RNA and protein from Tax + -T cells (TaxP) and Tax --T cells (TaxN) by using RT-PCR, qRT-PCR, and Western blot assays.…”

“…Oncoprotein Tax exhibits diverse functions in host cells, resulting in persistent activation of NF-κB and deregulation of its responsive gene expressions for T cell survival (Patrick et al, 2001;Easley et al, 2010;Alfonso et al, 2012). Tax protein predominantly localizes to the nucleus, However, Tax alone does not bind DNA; moreover, it functions as a transcriptional activator through interactions between the Tax and a large array of transcriptional regulators to regulate cellular processes (Boxus et al, 2008). Notably, the viral-transforming protein Tax is an important part of the oncogenic mechanism of HTLV-I in enhancing transcription by interacting with transcriptional factors.…”

Mechanisms of HTLV-1 persistence and transformation

“…To override regulatory functions of hDLG, TAX induces its hyperphosphorylation (Boxus et al, 2008). It is noteworthy that TAX mutants lacking the PBM are also impaired in immortalisation and transformation in vitro and in vivo (Xie et al, 2006).…”

“…The oncogenic potential of TAX is supported by its ability to immortalise cells in vitro, stimulate colony formation in soft agar and produce tumours in transgenic mouse models. Within the cell, TAX exerts its functions by complex formation with more than a hundred cellular proteins (Boxus et al, 2008). We recently proposed that the intrinsically disordered structure of TAX allows a wide variety of conformational changes enabling binding diversity and recognition of differently shaped protein partners.…”

“…Molecular mechanisms sustaining these TAX activities have been reviewed recently (Boxus et al, 2008). Depending on the model, TAX mutants defective for the activation of these pathways are poorly oncogenic both in vitro and in vivo.…”