# PROPERTIES OF A CARCINOGEN BINDING RECEPTOR-LIKE PROTEIN

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1987 · $126,063

## Abstract

The movement of foreign compounds, in particular the carcinogenic
polycyclic aromatic hydrocarbons, through an animal consists of a number of
complicated events.  The actual or potential steps of metabolic
transformation are reasonably well known, however, mechanisms of transport
of these highly lipophilic molecules, other than passive diffusion, are
virtually unknown.  Polycyclics also serve to induce new cytochrome P-450
activity, apparently at the transcriptional level, but again many of the
molecular details are unknown.  The ultimate fate of these compounds and
the actual biological residence time will greatly affect the compounds'
carcinogenic properties.  Also because they act as inducers of specific
isoenzymes of cytochrome P-450 the potential is high for the modulation of
their own carcinogenicity or that displayed by other environmental
pollutants in either a positive or negative direction.  The molecular
events of transport and induction then are integral to the understanding of
chemical carcinogenesis.  Preliminary studies have shown that a protein
exists in mouse liver cytosol that binds benzo[a]pyrene with high affinity
and in a pharmacologically specific fashion.  The concentration of this
protein and the dissociation constant (8nM) provide evidence that it may be
acting as an intracellular transport protein and/or a receptor involved in
cytochrome P-450 induction.  The goals in this project are to purify this
protein utilizing standard fractionation techniques, photoaffinity labels
and affinity chromatography.  The structural features important for ligand
binding will be studied by competition binding assays and a full kinetic
and thermodynamic characterization of the binding process will be studied.
By carrying out experiments of nuclear translocation and reversible
chemical crosslinking of the cytosol we will probe the nature of this
protein as a receptor and will observe molecular aspects of its activation
and transformation.  The relationship of this protein to the well
characterized Ah-receptor, a known receptor for cytochrome P-450 induction,
will be investigated.  These studies will hopefully provide greater
understanding of the carcinogenesis process itself.

## Key facts

- **NIH application ID:** 3175578
- **Project number:** 7R01CA037770-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** MICHAEL A. MARLETTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $126,063
- **Award type:** 7
- **Project period:** 1987-09-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175578

## Citation

> US National Institutes of Health, RePORTER application 3175578, PROPERTIES OF A CARCINOGEN BINDING RECEPTOR-LIKE PROTEIN (7R01CA037770-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175578. Licensed CC0.

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