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Transcriptional and cell cycle regulation after HTLV-1 infection.
Yoshida M; Department of Cellular and Molecular Biology,Institute of
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:168. Unique

HTLV-1 causes ATL, HAM/TSP, and uveitis. Transcription of HTVL-1 is activated by the viral protein Tax, which also activates expression of many specific cellular genes through two independent mechanisms. The Tax protein also binds to a cell cycle inhibitor and deregulates the cell cycle. (1) Tax activates the 21-bp enhancer of HTLV-1, NF-kappa B binding site, of the IL-2R alpha and SRE of the C-fos genes through binding to each binding protein. These enhancer proteins are CREB and CREM for the 21-bp enhancer , NF-kappa B p50, p52, p65, and c-Rel for the N[NF-kappa B] binding site and SRF for the SRE. Another mechanism of the transcriptional activation is include Tax binding to I kappa B proteins, inhibitors of NF-kappa B proteins. Tax binding to I kappa B proteins induces nuclear translocation of the active form of the NF-kappa B proteins. 2) Tax protein also binds to a cell cyclic inhibitor p16 and suppresses its inhibitory activity resulting in the activation of CDK4 kinase. The CDK4 activity phosphorylates Rb protein that negatively regulates the G1 progression of cells into S phase. The effect of Tax binding to p16 and activation of CDK4 on cellular proliferation will be discussed. 3) HTLV-1 genome is known to be exceptionally stable among retroviruses. However, we observed highly frequent and random mutations of the viral genome within individuals with HAM/TSP. Stable phenotype of the genome under the highly frequent mutations in vivo will be discussed.

Binding Sites *Cell Cycle Cyclin-Dependent Kinases/METABOLISM Enzyme Activation Gene Products, tax/METABOLISM HIV Infections/METABOLISM HTLV-I/GENETICS HTLV-I Infections/*GENETICS/PATHOLOGY Human Mutation NF-kappa B/METABOLISM Phosphorylation Retinoblastoma Protein/METABOLISM *Transcription, Genetic ABSTRACT

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