Tax1

Tax1 is a regulatory protein encoded by the tax gene of Human T‑Cell Leukemia Virus type 1 (HTLV‑1). The protein is a 353‑amino‑acid transcriptional transactivator that facilitates viral gene expression by binding to the long terminal repeat (LTR) promoter of the virus. Tax1 contains several functional domains: a leucine‑rich region, a nuclear localization signal, and multiple phosphorylation sites that regulate its stability and activity. Phosphorylation by protein kinase C and casein kinase II is required for full transactivation.

The protein’s primary role is to redirect host cellular transcription machinery. Tax1 recruits transcription factors such as CREB, NF‑κB, and AP‑1 to the viral promoter, thereby up‑regulating both viral and cellular genes. It also interacts with co‑activators p300/CBP and the mediator complex, enhancing transcriptional elongation. In addition to promoting viral replication, Tax1 activates signaling pathways that lead to cell proliferation, inhibition of apoptosis, and genomic instability. These activities contribute to the oncogenic potential of HTLV‑1 and are implicated in the development of adult T‑cell leukemia/lymphoma (ATL).

Tax1 is immunogenic and elicits robust cytotoxic T lymphocyte responses. Clinically, the detection of Tax1 RNA or protein in peripheral blood cells is used as a marker for active infection and disease progression. Because of its central role in viral replication and disease pathogenesis, Tax1 is a target for antiviral and therapeutic strategies. The Tax protein from HTLV‑2, known as Tax2, shares structural similarities but differs in several functional aspects and has a lower association with leukemogenesis.