The androgen receptor mRNA.
Androgens (testosterone), acting via the androgen receptor (AR) a nuclear transcription factor, regulate male sexual development and body composition. In addition, AR expression plays an important role in the proliferation of human prostate cancer and confers a better prognosis in breast cancer. AR mRNA stability is central to the regulation of AR expression in prostate and breast cancer cells, and recent studies have demonstrated binding by members of the ELAV/Hu and poly(C) RNA-binding protein families to a highly conserved UC-rich element in the 3'-untranslated region of AR mRNA, with functional impact on AR protein expression. Remarkably, a CAG trinucleotide repeat in exon 1 of the AR, the length of which has been linked to prostate cancer survival, is also a target for multiple RNA-binding proteins from a variety of human and murine tissues. In this review, we will detail the current knowledge of the mechanisms involved in regulating AR mRNA stability, the nature, potential role and structural biology of several novel AR mRNA-protein interactions, and the implications for novel therapeutics in human prostate cancer.
Yeap
Bu B
BB
School of Medicine and Pharmacology, The University of Western Australia, Fremantle and Royal Perth Hospitals, Perth, Western Australia, Australia.
Wilce
Jackie A
JA
Leedman
Peter J
PJ
D020816:Amino Acid Motifs; D000728:Androgens / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry; D011944:Receptors, Androgen / Q000378:metabolism*; D018911:Trinucleotide Repeats
D000728:Androgens; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen