Stabilization of wild-type p53 in human T-lymphocytes transformed by HTLV-I.
Adult T-cell leukemia/lymphoma is an aggressive malignancy associated with infection by the human T-lymphotropic virus type-I (HTLV-I). We now demonstrate that p53 expression is elevated in the HTLV-I-transformed T-lymphocyte lines C81, MT-2, MT-4 and HUT 102. In pulse-chase experiments, the p53 protein demonstrated a prolonged half-life of 2 to 8 h in HTLV-I-transformed cells compared with 0.5 to 1.0 h for wild-type p53 in primary human and murine fibroblasts, or human peripheral blood lymphocytes. In cell lines C81 and HUT 102, which exhibited the longest p53 protein half-life, the wild-type-related PAb1620 epitope was detected at reduced levels. The PAb240 mutant-related p53 epitope was not detected in any of the transformed cell lines. By direct sequence analysis of RT-PCR products, the entire p53 cDNA coding sequence was determined to be wild-type in all four cell lines. Stabilization of wild-type p53 may represent its functional inactivation and contribute to lymphocyte transformation by HTLV-I.
Reid
R L
RL
Laboratory of Molecular Virology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Lindholm
P F
PF
Mireskandari
A
A
Dittmer
J
J
Brady
J N
JN
D001483:Base Sequence; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004247:DNA / Q000737:chemistry; D006207:Half-Life; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D004247:DNA