A DNA-binding factor specific for xenobiotic responsive elements of P-450c gene exists as a cryptic form in cytoplasm: Its possible translocation to nucleus

Journal Article · Mon Aug 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.16.5859· OSTI ID:5564975

Fujisawa-Sehara, Atsuko; Yamane, Miyuki; Fujii-Kuriyama, Yoshiaki ^[1]

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1. Japanese Foundation for Cancer Research, Tokyo

Transcription of the drug-metabolizing cytochrome P-450c gene is induced by 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Previously, the authors defined two xenobiotic responsive elements (XREs) of {approx}15 base pairs, both of which activate transcription in cis in response to these xenobiotics. Using a gel mobility shift assay, they have identified a factor that specifically binds to the XREs. This factor appears in nuclei of mouse hepatoma cell line Hepa-1 only when the cells are treated with the xenobiotics, while the factor is undetectable in the nuclei of a 3-methylcholanthrene-treated mutant of Hepa-1 with defective function of a xenobiotic receptor. In addition, the nuclear factor bound to the XRE in the gel was found to be associated with ({sup 3}H)TCDD when the cells were treated with it, suggesting that the xenobiotic receptor is at least a component of the DNA-binding factor. The cytoplasmic fraction from nontreated Hepa-1 cells also contains the factor as a cryptic form and prominently reveals its DNA-binding activity by incubation with 3-methylcholanthrene in vitro. These results not only suggest the involvement of the XRE-binding factor in transcriptional activation via XREs but also provide evidence that the binding of ligands to the preexisting factor in a cryptic form induces its XRE-binding activity, which is probably followed by its translocation from cytoplasm to nucleus.

• OSTI ID: 5564975
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:16; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
3-METHYLCHOLANTHRENE
BIOLOGICAL EFFECTS
DIOXIN
TRANSCRIPTION
GENE REGULATION
CYTOCHROMES
CYTOPLASM
HEPATOMAS
TRITIUM COMPOUNDS
TUMOR CELLS
XENOBIOTICS
ANIMAL CELLS
AROMATICS
CELL CONSTITUENTS
DISEASES
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROGEN COMPOUNDS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PIGMENTS
POLYCYCLIC AROMATIC HYDROCARBONS
PROTEINS
550201* - Biochemistry- Tracer Techniques