The human T-cell leukemia virus type-1 (HTLV-1) infects CD4+ T-cells and is the etiological agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and often-fatal lymphoproliferative neoplastic disease. The major transactivator protein, Tax, drives proviral gene expression and replication and plays a key role during the early-stage immortalization of T-cells by HTLV-1. Tax has also been shown to regulate many host cellular signaling pathways, including CREB/ATF, SRF, and NFκB. Another accessory viral protein p30II acts as a latency-maintenance factor and negatively regulates proviral gene expression and replication. The p30II protein counters Tax-dependent gene expression at the transcriptional and posttranscriptional levels. HTLV-1 Tax constitutively activates the NFκB pathway. Intriguingly, the stathmin or OP18 (Oncoprotein-18) gene, a microtubule-destabilizing protein, is negatively regulated by p53/Sin3/HDAC1 repressor complexes and was recently shown to interact with and stabilize the p65RelA subunit of NFκB. Stathmin is associated with an aggressive disease phenotype in pancreatic cancers. Our lab has recently shown that p30II induces the expression of p53 dependent pro-survival genes such as TIGAR (Tp53 induced glycolysis and apoptosis regulator). In approximately half of all cancers, p53 is either mutated or functionally inactivated. However, in the majority of ATL patient isolates, the wildtype p53 protein continues to be expressed at high levels. My studies have demonstrated that the HTLV-1 p30II protein inhibits Stathmin expression in Tax-expressing HTLV-1 infected cells and ultimately suppresses NFκB hyperactivation. My research studies have revealed that Stathmin/Op-18 might act as an important co-factor for NFκB-activation in HTLV-1 associated oncogenesis and highlights the cooperative role of the latency-maintenance factor, p30II, with the viral transactivator by preventing Tax-induced cytotoxicity and genomic instability and may allow for the continued proliferation of HTLV-1 transformed cells and conceivably aid in disease progression. Overall my research work reveals a mechanistic link between NFκB inflammatory signaling and genomic instability that may contribute to oncogenesis and transformation in certain human cancers.

Degree Date

Spring 5-18-2019

Document Type


Degree Name



Biological Sciences


Robert Harrod

Subject Area

Cell Biology, Molecular Biology

Number of Pages




Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License