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The HTLV-1 Tax interactome.

Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L - Retrovirology (2008)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: University Academia Wallonie-Europe, Molecular and Cellular Biology at FUSAGx, Gembloux, Belgium. boxus.m@fsagx.ac.be

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.

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Global model of Tax1 mediated transactivation. Tax1 relieves transcriptional repression of the LTR through direct interaction with HDAC (i.e. HDAC1) and/or HMT (panel A). Tax1 recruits CREB/ATF transcription factors (CA in panel B), histone modifying enzymes and chromatin remodelers (SWI/SNF, P/CAF and CBP/p300). Tax1 then allows binding of basal transcription factors on the TATA box (panel C). Once the initiation complex is formed, Tax1 recruits the P-TEFb factor, leading to CTD phosphorylation and processive elongation (panel D). Finally, interaction of Tax1 with SWI/SNF prevents stalling of transcription elongation. Adapted from [120,132,138,316].
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Figure 1: Global model of Tax1 mediated transactivation. Tax1 relieves transcriptional repression of the LTR through direct interaction with HDAC (i.e. HDAC1) and/or HMT (panel A). Tax1 recruits CREB/ATF transcription factors (CA in panel B), histone modifying enzymes and chromatin remodelers (SWI/SNF, P/CAF and CBP/p300). Tax1 then allows binding of basal transcription factors on the TATA box (panel C). Once the initiation complex is formed, Tax1 recruits the P-TEFb factor, leading to CTD phosphorylation and processive elongation (panel D). Finally, interaction of Tax1 with SWI/SNF prevents stalling of transcription elongation. Adapted from [120,132,138,316].

Mentions: Most of the data summarized in the former paragraphs relate to transcriptional activation of the LTR by Tax1 although it is likely that similar mechanisms also pertain to cellular promoters. Figure 1 recapitulates the mechanisms of transactivation: Tax1 relieves transcriptional repression through direct interaction with HDAC (i.e. HDAC1) and/or HMT (panel A). Tax1 interacts with CREB/ATF factors (CA) and enhances their binding to the LTR (panel B). When complexes are stabilized on the promoter, Tax1 recruits histone modifying enzymes and chromatin remodelers. This step affects chromatin structure and allows binding of basal transcription factors on the TATA box that is further stabilized by Tax1 interaction with TFIIA, TFIID and TBP (panel C). Once the initiation complex is formed, Tax1 recruits the P-TEFb factor, leading to CTD phosphorylation and processive elongation (panel D). Finally, interaction of Tax1 with SWI/SNF prevents stalling of transcription elongation.


The HTLV-1 Tax interactome.

Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L - Retrovirology (2008)

Global model of Tax1 mediated transactivation. Tax1 relieves transcriptional repression of the LTR through direct interaction with HDAC (i.e. HDAC1) and/or HMT (panel A). Tax1 recruits CREB/ATF transcription factors (CA in panel B), histone modifying enzymes and chromatin remodelers (SWI/SNF, P/CAF and CBP/p300). Tax1 then allows binding of basal transcription factors on the TATA box (panel C). Once the initiation complex is formed, Tax1 recruits the P-TEFb factor, leading to CTD phosphorylation and processive elongation (panel D). Finally, interaction of Tax1 with SWI/SNF prevents stalling of transcription elongation. Adapted from [120,132,138,316].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2533353&req=5

Figure 1: Global model of Tax1 mediated transactivation. Tax1 relieves transcriptional repression of the LTR through direct interaction with HDAC (i.e. HDAC1) and/or HMT (panel A). Tax1 recruits CREB/ATF transcription factors (CA in panel B), histone modifying enzymes and chromatin remodelers (SWI/SNF, P/CAF and CBP/p300). Tax1 then allows binding of basal transcription factors on the TATA box (panel C). Once the initiation complex is formed, Tax1 recruits the P-TEFb factor, leading to CTD phosphorylation and processive elongation (panel D). Finally, interaction of Tax1 with SWI/SNF prevents stalling of transcription elongation. Adapted from [120,132,138,316].
Mentions: Most of the data summarized in the former paragraphs relate to transcriptional activation of the LTR by Tax1 although it is likely that similar mechanisms also pertain to cellular promoters. Figure 1 recapitulates the mechanisms of transactivation: Tax1 relieves transcriptional repression through direct interaction with HDAC (i.e. HDAC1) and/or HMT (panel A). Tax1 interacts with CREB/ATF factors (CA) and enhances their binding to the LTR (panel B). When complexes are stabilized on the promoter, Tax1 recruits histone modifying enzymes and chromatin remodelers. This step affects chromatin structure and allows binding of basal transcription factors on the TATA box that is further stabilized by Tax1 interaction with TFIIA, TFIID and TBP (panel C). Once the initiation complex is formed, Tax1 recruits the P-TEFb factor, leading to CTD phosphorylation and processive elongation (panel D). Finally, interaction of Tax1 with SWI/SNF prevents stalling of transcription elongation.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: University Academia Wallonie-Europe, Molecular and Cellular Biology at FUSAGx, Gembloux, Belgium. boxus.m@fsagx.ac.be

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.

Show MeSH
Related in: MedlinePlus