Molecular interactions between the HTLV-1 Tax oncoprotein and the NF-kappa B-kappa B/I-kappa B regulatory proteins (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Molecular interactions between the HTLV-1 Tax oncoprotein and the NF-kappa B-kappa B/I-kappa B regulatory proteins (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A3145 1995. Unique Identifier : AIDSLINE ICDB/95610918
Hiscott J; Lacoste J; Crepieux P; Petropoulos L; Jackson D; Beauparlant P; Pepin N; Lin R; Lady Davis Inst., McGill Univ., Montreal, Quebec H3T 1E2, Canada

Abstract: Human T-cell leukemia virus type 1 (HTLV-I) is the etiologic agent of adult T-cell leukemia, an aggressive and fatal leukemia of CD4+ T cells. The oncogenic potential of HTLV-I resides in the 40-kD viral Tax oncoprotein which has been characterized as a strong trans-activator of viral transcription. One of the targets of interaction for Tax protein is the NF-kappa B transcription complex, a family of regulatory proteins involved in immunoregulation and cellular growth control. Recent studies demonstrated that Tax protein physically associated with specific NF-kappa B and I-kappa B subunits leading to gene trans-activation, subcellular redistribution of Tax protein and a Tax-mediated increase in NF-kappa B dimerization. Tax also increased phosphorylation and proteolytic degradation of the inhibitor I-kappa B alpha. In complementary studies, disruption of I-kappa B alpha autoregulation using antisense RNA or I-kappa B alpha overexpression dramatically altered cellular growth, suggesting that I-kappa B alpha may represent a negative growth regulator. A kinase activity was isolated from Jurkat cells that specifically bound to I-kappa B alpha in a GST affinity step and phosphorylated I-kappa B alpha in vitro with high specificity in the C-terminal PEST domain. These studies indicate that I-kappa B may represent a potential tumor suppressor activity and that Tax and NF-kappa B/I-kappa B interactions may disrupt NF-kappa B mediated gene expression, leading to T-cell leukemogenesis.

Keywords: Cell Division Cell Line Cell Transformation, Neoplastic DNA-Binding Proteins/BIOSYNTHESIS/*METABOLISM Gene Expression Gene Products, tax/*METABOLISM Human HTLV-I/*METABOLISM Macromolecular Systems Proto-Oncogene Proteins/*METABOLISM RNA, Antisense/PHARMACOLOGY Trans-Activation (Genetics) Transcription, Genetic Tumor Cells, Cultured ABSTRACT
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