The poly(c)-binding protein-1 regulates expression of the androgen receptor.
The androgen receptor (AR) is a ligand-dependent transcription factor, expressed in male and female reproductive organs, and essential for normal reproduction in both sexes. The levels of AR are tightly controlled in androgen-responsive cells in which it plays a central role in the regulation of target gene expression. The AR is abundantly expressed in human endometrial stromal cells (HESCs), but levels decline markedly after differentiation into decidual cells in vivo and in primary cultures. Decidualization profoundly down-regulated AR protein levels with no discernible effect on either AR mRNA or protein stability, suggesting that loss of the receptor was a consequence of translational inhibition. Here we show that HESCs express three RNA-binding proteins, Hu antigen R and the poly(C)-binding proteins PCBP1 and PCBP2, that reportedly target the 3'-untranslated region of AR transcripts. Only PCBP1 expression was enhanced in secretory endometrium in vivo and in decidualizing HESCs. Furthermore, knockdown of PCBP1 in decidualizing cells was sufficient to restore AR protein levels, indicating that loss of the AR protein is primarily the consequence of a translational block. PCBP1 also blocked AR translation in a cell-free system, although this did not require binding to the 3'-untranslated region of the receptor mRNA. Furthermore, knockdown of PCBP1 in the prostate cancer LNCaP cell line also increased AR protein. Therefore, PCBP1 plays a major role in the dynamic expression of AR in both male and female androgen-responsive cells.
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK.
Brianna
B
Cloke
Kunal
K
Shah
Hiroshi
H
Kaneda
Stuart
S
Lavery
Geoffrey
G
Trew
Luca
L
Fusi
Jenny
J
Higham
Roberto E
RE
Dina
Sadaf
S
Ghaem-Maghami
Patricia
P
Ellis
Jan J
JJ
Brosens
Mark
M
Christian
D000293:Adolescent; D000328:Adult; D059002:Androgen Receptor Antagonists; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics; D004268:DNA-Binding Proteins; D004717:Endometrium / Q000378:metabolism / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology; D055815:Young Adult
D059002:Androgen Receptor Antagonists; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C094604:PCBP1 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases