RRC ID 34783
Author Shoji T, Higuchi M, Kondo R, Takahashi M, Oie M, Tanaka Y, Aoyagi Y, Fujii M.
Title Identification of a novel motif responsible for the distinctive transforming activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2 Tax2.
Journal Retrovirology
Abstract BACKGROUND:Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia (ATL), whereas its relative HTLV-2 is not associated with any malignancies including ATL. HTLV-1 Tax1 transformed a T-cell line from interleukin (IL)-2-dependent growth to IL-2-independent growth, with an activity that was much more potent in comparison to HTLV-2 Tax2. This distinction was mediated by at least two Tax1 specific functions, an interaction with host cellular factors through the PDZ domain binding motif (PBM) and the activation of NF-kappa B2 (NF-kappa B2)/p100.
RESULTS:Using a series of Tax1 chimeric proteins with Tax2, we found that amino acids 225-232 of Tax1, the Tax1(225-232) region, was essential for the activation of NF-kappa B2 as well as for the high transforming activity. The strict amino acid conservation of Tax1(225-232) among HTLV-1 and simian T-cell leukemia virus type 1 (STLV-1), but not HTLV-2 and STLV-2, indicates that function(s) through the Tax1(225-232) region are biologically significant. Interestingly, another HTLV-1 relative, HTLV-3, has a PBM, but does not conserve the Tax1(225-232) motif in Tax3, thus indicating that these two motifs classify the three HTLVs into the separate groups.
CONCLUSION:These results suggest that the combinatory functions through Tax1(225-232) and PBM play crucial roles in the distinct biological properties of the three HTLVs, perhaps also including their pathogenesis.
Volume 6
Pages 83
Published 2009-9-17
DOI 10.1186/1742-4690-6-83
PII 1742-4690-6-83
PMID 19761585
PMC PMC2754985
MeSH Amino Acid Motifs Animals Cell Line Cell Transformation, Viral* Conserved Sequence Gene Products, tax / genetics Gene Products, tax / metabolism* Human T-lymphotropic virus 1 / genetics Human T-lymphotropic virus 1 / pathogenicity* Human T-lymphotropic virus 2 / genetics Human T-lymphotropic virus 2 / pathogenicity* Humans Leukemia, T-Cell / virology Mice NF-kappa B / biosynthesis Primate T-lymphotropic virus 3 / genetics Recombinant Proteins Simian T-lymphotropic virus 1 / genetics T-Lymphocytes / virology*
IF 4.183
Times Cited 40
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)