PATZ attenuates the RNF4-mediated enhancement of androgen receptor-dependent transcription.
PATZ is a transcriptional repressor affecting the basal activity of different promoters, whereas RNF4 is a transcriptional activator. The association of PATZ with RNF4 switches the activation to repression of selected basal promoters. Because RNF4 interacts also with the androgen receptor (AR) functioning as a coactivator and, in turn, RNF4 associates with PATZ, we investigated whether PATZ functions as an AR coregulator. We demonstrate that PATZ does not influence directly the AR response but acts as an AR corepressor in the presence of RNF4. Such repression is not dependent on histone deacetylases. A mutant RNF4 that does not bind PATZ but enhances AR-dependent transcription is not influenced by PATZ, demonstrating that the repression by PATZ occurs only upon binding to RNF4. We also demonstrate that RNF4, AR, and PATZ belong to the same complex in vivo also in the presence of androgen, suggesting that repression is not mediated by the displacement of RNF4 from AR. Finally, we show that the repression of endogenous PATZ expression by antisense expression plasmids in LNCaP cells results in a stronger androgen response. Our findings demonstrate that PATZ is a novel AR coregulator that acts by modulating the effect of a coactivator. This could represent a novel and more general mechanism to finely tune the androgen response.
Pero
Raffaela
R
Centro di Endocrinologia ed Oncologia Sperimentale del CNR "G. Salvatore," Dipartimento di Biologia e Patologia Cellulare e Molecolare, "L. Califano" Università degli Studi di Napoli "Federico II," via S. Pansini, 5, 80131 Napoli, Italy.
Lembo
Francesca
F
Palmieri
Emiliano Antonio
EA
Vitiello
Carmen
C
Fedele
Monica
M
Fusco
Alfredo
A
Bruni
Carmelo Bruno
CB
Chiariotti
Lorenzo
L
D000818:Animals; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000235:genetics; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C412784:PATZ1 protein, human; C114070:RNF4 protein, human; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D013196:Dihydrotestosterone; D008156:Luciferases