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Details for Patent: 5,552,271

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Details for Patent: 5,552,271

Title: RXR homodimer formation
Abstract:The invention provides a method of screening a substance for the ability to effect the formation of a retinoid X receptor homodimer comprising combining the substance and a solution containing retinoid X receptors and determining the presence of homodimer formation. Also provided is a method of screening a substance for an effect on a retinoid X receptor homodimer's ability to bind DNA comprising combining the substance with the homodimer and determining the effect of the compound on the homodimer's ability to bind DNA. A method of inhibiting an activity of a retinoid X receptor heterodimer comprising increasing the formation of a retinoid X receptor homodimer, thereby preventing the retinoid X receptor from forming a heterodimer and preventing the resulting heterodimer activity is also provided. A method of inhibiting an activity of a retinoid X receptor homodimer is also provided. In addition, a method of screening a response element for binding with a retinoid X receptor homodimer is provided. Finally, the invention provides methods of activating retinoid X receptor homodimer formation.
Inventor(s): Pfahl; Magnus (Solana Beach, CA), Zhang; Xiao-kun (La Jolla, CA), Lehmann; J urgen M. (Solana Beach, CA), Dawson; Marcia I. (Menlo Park, CA), Cameron; James F. (Palo Alto, CA), Hobbs; Peter D. (Moss Beach, CA), Jong; Ling (Sunnyvale, CA)
Assignee: La Jolla Cancer Research Foundation (La Jolla, CA)
Filing Date:Nov 25, 1992
Application Number:07/982,174
Claims:1. A method of screening a substance for the ability to selectively induce the formation of a retinoid X receptor homodimer over a retinoid X receptor heterodimer comprising:

a. combining in a cell expressing a retinoid X receptor vector the substance to be screened and a second receptor capable of forming a retinoid X receptor heterodimer;

b. determining by cotransfection and expression of a response element linked reporter gene (1) if the substance induces a retinoid X receptor heterodimer, and (2) if the substance induces the formation of a retinoid X receptor homodimer; and

c. selecting the substance which selectively induces the formation of a retinoid X receptor homodimer.

2. The method of claim 1, wherein the heterodimer is a retinoid X receptor and retinoic acid receptor.

3. A method of screening a substance for the ability to selectively induce a retinoid X receptor homodimer over a retinoid X receptor heterodimer comprising:

a. combining the retinoid X receptor with the substance to be screened and a second receptor capable of forming a retinoid X receptor heterodimer;

b. determining by co-precipitation (1) if the substance induces the formation of a retinoid X receptor homodimer, and (2) if the substance induces a retinoid X receptor heterodimer; and

c. selecting the substance which selectively induces the formation of a retinoid X receptor homodimer.

4. A method of screening a substance for the ability to selectively induce a retinoid X receptor homodimer over a retinoid X receptor heterodimer in solution comprising:

a. combining the retinoid X receptor with the substance to be screened and a second receptor capable of forming a retinoid X receptor heterodimer, wherein the second receptor is not a retinoid acid receptor .beta.;

b. determining by gel shift assay (1) if the substance induces the formation of a retinoid X receptor homodimer, and (2) if the substance induces a retinoid X receptor heterodimer; and

c. selecting the substance which selectively induces the formation of a retinoid X receptor homodimer.
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