Functional inactivation of wild-type p53 protein correlates with loss of IL-2 dependence in HTLV-I transformed human T lymphocytes.
Human T cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T cell leukemia (ATL) transforms human T cells in vitro and in vivo. Tax, the major transactivator of HTLV-I is critical for the initial events involved in transformation, however, the later steps required for progression from an IL-2 dependent state to one of IL-2 independence remain to be clarified. We investigated the potential role of p53 protein in this process employing several IL-2 dependent and independent HTLV-I transformed cell lines. All cell lines examined were found to be wild-type in the p53 coding region usually associated with inactivating mutations using RT-PCR-SSCP analysis and DNA sequencing. Levels of p53 protein were consistently higher in IL-2 independent lines compared to IL-2 dependent ones. Lack of functional p53 activity was observed only in IL-2 independent cell lines using a transfection assay with a B-galactosidase reporter gene construct responsive to wild-type p53 protein. Increased steady state levels of wild-type p53 protein associated with its functional inactivation appear to be linked to the loss of IL-2 dependent growth in HTLV-I transformed lymphocytes.
Gartenhaus
R B
RB
Division of Hematology/Oncology, Long Island Jewish Medical Center, NY, USA.
Wang
P
P
D001483:Base Sequence; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D007376:Interleukin-2; D016159:Tumor Suppressor Protein p53