Abstract |
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.
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Authors | Y Hashimoto, K Shudo |
Journal | Japanese journal of cancer research : Gann
(Jpn J Cancer Res)
Vol. 82
Issue 6
Pg. 665-75
(Jun 1991)
ISSN: 0910-5050 [Print] Japan |
PMID | 1906853
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carcinogens
- Heat-Shock Proteins
- Protein Kinase C
- Tetradecanoylphorbol Acetate
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Topics |
- Carcinogens
(metabolism)
- Cell Nucleus
(metabolism)
- Chromatography, High Pressure Liquid
- Cytosol
(metabolism)
- HeLa Cells
(drug effects, metabolism)
- Heat-Shock Proteins
(isolation & purification, metabolism)
- Humans
- Kinetics
- Molecular Structure
- Molecular Weight
- Protein Kinase C
(metabolism)
- Structure-Activity Relationship
- Tetradecanoylphorbol Acetate
(metabolism, pharmacology)
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