Back to Search
Start Over
Novel Binding of HuR and Poly(C)-binding Protein to a Conserved UC-rich Motif within the 3′-Untranslated Region of the Androgen Receptor Messenger RNA
- Source :
- Journal of Biological Chemistry. 277:27183-27192
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- The androgen receptor (AR) mediates androgen action and plays a central role in the proliferation of specific cancer cells. We demonstrated recently that AR mRNA stability is a major determinant of AR gene expression in prostate and breast cancer cells and that androgens differentially regulate AR mRNA decay dependent on cell type (Yeap, B. B., Kreuger, R. G., Leedman, P. J. (1999) Endocrinology 140, 3282-3291). Here, we have identified a highly conserved UC-rich region in the 3-untranslated region of AR mRNA that contains a 5'-C(U)(n)C motif and a 3'-CCCUCCC poly(C)-binding protein motif. In transfection studies with LNCaP human prostate cancer cells, the AR UC-rich region reduced expression of a luciferase reporter gene. The AR UC-rich region was a target for cytoplasmic and nuclear RNA-binding proteins from human prostate and breast cancer cells as well as human testicular and breast cancer tissue. One of these proteins is HuR, a ubiquitously expressed member of the Elav/Hu family of RNA-binding proteins involved in the stabilization of several mRNAs. Poly(C)-binding protein-1 and -2 (CP1 and CP2), previously implicated in the control of mRNA turnover and translation, also bound avidly to the UC-rich region. Mutational analysis of the UC-rich region identified specific binding motifs for both HuR and the CPs. HuR and CP1 bound simultaneously to the UC-rich RNA and in a cooperative manner. Immunoprecipitation studies confirmed that each of these proteins associated with AR mRNA in prostate cancer cells. In summary, we have identified and characterized a novel complex of AR mRNA-binding proteins that target the highly conserved UC-rich region. The binding of HuR, CP1, and CP2 to AR mRNA suggests a role for each of these proteins in the post-transcriptional regulation of AR expression in cancer cells.
- Subjects :
- Cytoplasm
Recombinant Fusion Proteins
Amino Acid Motifs
ELAV-Like Protein 1
Biology
Transfection
Heterogeneous ribonucleoprotein particle
Biochemistry
Heterogeneous-Nuclear Ribonucleoproteins
Mice
Gene expression
LNCaP
Tumor Cells, Cultured
Animals
Humans
RNA, Messenger
Luciferases
3' Untranslated Regions
Molecular Biology
Glutathione Transferase
Cell Nucleus
AU-rich element
Messenger RNA
Dose-Response Relationship, Drug
Reverse Transcriptase Polymerase Chain Reaction
Three prime untranslated region
RNA-Binding Proteins
Cell Biology
Precipitin Tests
Molecular biology
Rats
DNA-Binding Proteins
Androgen receptor
Cross-Linking Reagents
ELAV Proteins
Receptors, Androgen
Antigens, Surface
Cell Division
Plasmids
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 277
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....a4e0907ffd0692b3026987f1e7847325