Recently, Dr. Zongping Xia’s lab at the Life Sciences Institute, Zhejiang University published their new findings at PLoS Pathogens. The paper is entitled “HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains”.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM), a distinct neurological disorder with inflammatory symptoms and incomplete paralysis of the limbs, and adult T-cell leukemia/lymphoma (ATL), a highly aggressive malignant proliferation of CD4+ T lymphocytes. Both TSP/HAM and ATL are mainly driven by the activation of IκB kinase (IKK)-NF-κB stimulated by HTLV-1 oncoprotein Tax. The molecular mechanism by which Tax activates IKK remains unclear.

Here, Dr. Xia’s groupfound that Tax is an E3 ubiquitin ligase, which, together with its cognate ubiquitin-conjugating enzymes (E2s) UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of unanchored free mixed-linkage polyubiquitin chains. The polyubiquitin chains can activate IKK complex directly by binding to the NEMO subunit. Thisstudyuncovered the essential cellular factors hijacked by HTLV-1 for infection and pathogenesis, as well as the biochemical function and the underlying mechanism of Tax in the process of IKK activation. This work might shed light on potential development of therapeutics for TSP/HAM and ATL.

Model illustrating IKK-NF-κB activation by Tax.

Text link: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005584