Advertisement

 

 

HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains.

Author Information (click to view)

Wang C, Long W, Peng C, Hu L, Zhang Q, Wu A, Zhang X, Duan X, Wong CC, Tanaka Y, Xia Z,


Wang C, Long W, Peng C, Hu L, Zhang Q, Wu A, Zhang X, Duan X, Wong CC, Tanaka Y, Xia Z, (click to view)

Wang C, Long W, Peng C, Hu L, Zhang Q, Wu A, Zhang X, Duan X, Wong CC, Tanaka Y, Xia Z,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

PLoS pathogens 2016 4 1512(4) e1005584 doi 10.1371/journal.ppat.1005584

Abstract

The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.

Submit a Comment

Your email address will not be published. Required fields are marked *

five + nineteen =

[ HIDE/SHOW ]