Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination.
The androgen receptor (AR) plays a critical role in prostate cancer. We have identified a ubiquitin E3 ligase, RNF6, as an AR-associated protein in a proteomic screen. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of RNF6 or mutation of RNF6-induced ubiquitination acceptor sites on AR selectively ... alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen-responsive elements present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our data suggest that RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment.
Mesh Terms:
Amino Acid Sequence, Androgens, Animals, COS Cells, Cells, Cultured, Cercopithecus aethiops, Chromatin Immunoprecipitation, DNA-Binding Proteins, Fluorescent Antibody Technique, Gene Expression Profiling, Humans, Immunoenzyme Techniques, Kidney, Male, Molecular Sequence Data, Neoplasms, Hormone-Dependent, Prostatic Hyperplasia, Prostatic Neoplasms, RNA, Messenger, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Transcription, Genetic, Ubiquitination
Amino Acid Sequence, Androgens, Animals, COS Cells, Cells, Cultured, Cercopithecus aethiops, Chromatin Immunoprecipitation, DNA-Binding Proteins, Fluorescent Antibody Technique, Gene Expression Profiling, Humans, Immunoenzyme Techniques, Kidney, Male, Molecular Sequence Data, Neoplasms, Hormone-Dependent, Prostatic Hyperplasia, Prostatic Neoplasms, RNA, Messenger, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Transcription, Genetic, Ubiquitination
Cancer Cell
Date: Apr. 07, 2009
PubMed ID: 19345326
View in: Pubmed Google Scholar
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