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.

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].

Figure 2

Overview of cell signaling proteins targeted by Tax1. Tax1 interacts with components of several signaling pathways (MAPK, JNK, NF-κB, AP-1 and TGF-β) and promotes cellular activation, proliferation, cytoskeleton rearrangement, cell migration and formation of the virological synapse.

Figure 3

Effect of Tax1 on cell cycle progression. Through a series of interactions with cell-cycle associated proteins, Tax1 accelerates G1/S transition (A), attenuates Chk1/2 activity (B), induces supernumerary centrosomes and impedes SAC (spindle assembly checkpoint) activity (C).

Figure 4

Functional regions of Tax1 and interaction domains. NLS (nuclear localization sequence), NES (nuclear export sequence), G (Golgi localization motif), S (secretion motif), LZR (leucine-zipper-like region), P (PDZ binding domain). Adapted from [130].

Figure 5

Overview of the Tax1 interactome.

Figure 6

Identification of disordered regions in Tax1 according to the VSL1 algorithm. (PONDR^®, ). A domain encompassing residues 76 to 121 (black bar) corresponds to a long disordered region within Tax1.