The human T-cell leukemia virus type-1 tax oncoprotein dissociates NF- κB p65RelA-Stathmin complexes and causes catastrophic mitotic spindle damage and genomic instability.

The human T-cell leukemia virus type-1 tax oncoprotein dissociates NF-κB p65RelA-Stathmin complexes and causes catastrophic mitotic spindle damage and genomic instability. Virology. 2019 Jul 03;535:83-101 Authors: Malu A, Hutchison T, Yapindi L, Smith K, Nelson K, Bergeson R, Pope J, Romeo M, Harrod C, Ratner L, Van Lint C, Harrod R Abstract Genomic instability is a hallmark of many cancers; however, the molecular etiology of chromosomal dysregulation is not well understood. The human T-cell leukemia virus type-1 (HTLV-1) oncoprotein Tax activates NF-κB-signaling and induces DNA-damage and aberrant chromosomal segregation through diverse mechanisms which contribute to viral carcinogenesis. Intriguingly, Stathmin/oncoprotein-18 (Op-18) depolymerizes tubulin and interacts with the p65RelA subunit and functions as a cofactor for NF-κB-dependent transactivation. We thus hypothesized that the dissociation of p65RelA-Stathmin/Op-18 complexes by Tax could lead to the catastrophic destabilization of microtubule (MT) spindle fibers during mitosis and provide a novel mechanistic link between NF-κB-signaling and genomic instability. Here we report that the inhibition of Stathmin expression by the retroviral latency protein, p30II, or knockdown with siRNA-stathmin, dampens Tax-mediated NF-κB transactivation and counters Tax-induced genomic instability and cytotoxicity. The Tax-G148V mutant, defective for NF-κB activation, exhibited reduced...
Source: Virology - Category: Virology Authors: Tags: Virology Source Type: research