Androgen receptor coactivators
Disclosed are androgen receptor-associated proteins, designated ARA24, ARA54, ARA55, and Rb, that have been demonstrated to interact with the androgen receptor to alter levels of androgen receptor-mediated transcriptional activation. Certain of these proteins interact with the androgen receptor in an androgen-dependent manner, whereas certain proteins may induce transcriptional activation in the presence of other ligands, such as E2 or HF. Also disclosed is a method of detecting androgenic or antiandrogenic activity using these proteins in a mammalian two-hybrid transient transfection assay.
1. An isolated polynucleotide comprising the sequence set forth in SEQ ID NO:3.
2. An isolated polynucleotide comprising a promoter capable of causing expression of a protein coding region in a cell, the promoter operably connected to a protein coding region of a polypeptide set forth in SEQ ID NO:4.
3. The isolated polynucleotide of claim 2 wherein the protein coding region comprises a sequence set forth in SEQ ID NO: 3.
4. A eukaryotic host cell comprising the isolated polynucleotide of claim 2 .
5. An isolated polynucleotide encoding an ARA55 polypeptide comprising amino acids 251–444 of SEQ ID NO: 4 and a LIM motif, wherein the ARA55 polypeptide enhances the transcription activity of an Androgen Receptor.
6. The isolated polynucleotide of claim 5 , wherein the ARA55 polypeptide enhances the transcription activity of an Androgen Receptor at least 4 fold.
7. The isolated polynucleotide claim 5 , wherein the ARA55 polypeptide enhances the transcription activity of an Androgen Receptor at least 8 fold.
8. The isolated polynucleotide of claim 5 , wherein the enhancement comprises an interaction between 17 β estradiol (E2) and a mutant Androgen Receptor.
9. The isolated polynucleotide of claim 5 , wherein the enhancement comprises an interaction between hydroxyflutamide (HF) and a mutant Androgen Receptor.
10. The isolated polynucleotide of claim 5 , wherein the enhancement comprises an interaction between dihydrotestosterone (DHT) and a mutant Androgen Receptor.
11. An isolated polynucleotide encoding an ARA55 polypeptide comprising amino aids 251–444 of SEQ ID NO: 4 and a protein called a LIM motif, wherein the ARA55 polypeptide enhances the transcriptional activity of a mutant Androgen Receptor.
12. The isolated polynucleotide of claim 11 , wherein the enhancement comprises an interaction between 17 β estradiol (E2) and the mutant Androgen Receptor.
13. The isolated polynucleotide of claim 11 , wherein the enhancement comprises an interaction between hydroxyflutamide (HF) and the mutant Androgen Receptor.
14. The isolated polynucleotide of claim 11 , wherein the enhancement comprises an interaction between dihydrotestosterone (DHT) and the mutant Androgen Receptor.
15. The isolated polynucleotide of claim 11 , wherein the enhancement comprises an interaction between testosterone (T) and the mutant Androgen Receptor.
16. An isolated polynucleotide encoding an ARA55 polypeptide comprising amino acids 251–444 of SEQ ID NO: 4, wherein the ARA55 polypeptide inhibits the transcription activity of an Androgen Receptor.