Setting the stage for transformation: HTLV-1 Tax inhibition of p53 function.
Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Although the precise mechanism of HTLV-1 oncogenesis remains unclear, the pathogenesis has been linked to the pleiotropic activity of the viral transcriptional activator protein Tax. Tax has been shown to regulate viral and cellular gene expression and to functionally interfere with proteins involved in cell-cycle progression and DNA repair. This review will concentrate on the ability of Tax to promote cellular proliferation through activation of the NF-kappaB pathway while inhibiting the cell-cycle checkpoint and apoptotic function of the tumor suppressor gene p53.
Pise-Masison
Cynthia A
CA
Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 41 Room B201, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Brady
John N
JN
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004260:DNA Repair; D016356:Gene Products, tax / Q000737:chemistry* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D020079:Terminal Repeat Sequences; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016356:Gene Products, tax; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53