Inhibition of binding of Hox and homeodomain-containing proteins and uses thereof
AssigneeThe UAB Research Foundation
InventorsXu Cao, Xingming Shi, Xiangli Yang
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Abstract
The present invention demonstrates that BMP-2/4 activates osteopontin gene transcription by removing Hoxc-8 binding through Smad1 interaction with the Hoxc-8 DNA binding domain. Since the DNA binding domain is conserved in all Hox and homeodomain-containing proteins, Smad1 likely interacts with all Hox or homeodomain-containing proteins. Furthermore, the present invention reveals the Smad1-mediated transcriptional mechanism in the BMP-2/4 signaling pathway and also provides information about the transcriptional roles of the Hox genes during embryonic development.
Claims6
A method of inducing the expression of genes that contain Hox protein binding elements and encode bone matrix proteins in vitro, comprising the step of:
- transfecting an expression plasmid encoding Smad1 into a cell, wherein said expressed Smad1 interacts with Hox protein and inhibits the binding of said Hox protein to DNA, thereby inducing the expression of genes that contain Hox protein binding elements.
A method of inducing the expression of a gene encoding osteopontin, comprising the step of:
- transfecting expression plasmid encoding Smad1 into a cell, wherein said expressed Smad1 interacts with Hoxc-8 protein and inhibits the binding of said Hoxc-8 protein to DNA, thereby inducing the expression of said gene encoding osteopontin.
A method of screening for a compound that stimulates bone formation, comprising the steps of:
- contacting a cell with a compound;
- and
- determining the ability of said compound to inhibit binding of Hoxc-8 to a gene, wherein inhibition of binding results in induction of said gene, thus indicating that the compound stimulates bone formation.
Dependencies are inferred from the claim text.