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‐tetradecanoyl‐phorbol 13‐acetate (TPA). The translation 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 1.4X10(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.