Cytosolic-nuclear tumor promoter-specific binding protein: association with the 90 kDa heat shock protein and translocation into nuclei by treatment with 12-O-tetradecanoylphorbol 13-acetate.
Suspension-cultured HeLa cells possess a cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) which lacks protein kinase C activity. This CN-TPBP existed in cytosol of HeLa cells, but translocated into nuclear fraction of the cells after treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate (TPA). The translocation of CN-TPBP induced by TPA became apparent within 10 min after the treatment with TPA, and was completed within 3 h. CN-TPBP bound TPA with the association constant of 1.4 x 10(10) M-1, and also bound teleocidin B, debromoaplysiatoxin, and thapsigargin in a mutually competitive manner. The binding affinity order of synthetic analogs of teleocidin B correlated with the adhesion-inducing potency order of the compounds toward human leukemia cell line HL-60. The apparent molecular weight of CN-TPBP under non-denaturing conditions was estimated to be 66-68 kDa. CN-TPBP forms a complex with the 90 kDa heat shock protein, and the complex was stabilized by the presence of molybdate. These characteristics of CN-TPBP are similar to those of the nuclear receptors of glucocorticoid and dioxin. These findings suggested that CN-TPBP acts as a nuclear receptor for tumor promoters, and that tumor promoters may exert their biological effects by binding to CN-TPBP.
Hashimoto
Y
Y
Institute of Applied Microbiology, University of Tokyo.
Shudo
K
K
D002273:Carcinogens / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D008970:Molecular Weight; D011493:Protein Kinase C / Q000378:metabolism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology*
D002273:Carcinogens; D006360:Heat-Shock Proteins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate