Characterization of receptor-interacting protein RIP140 in the regulation of SF-1 responsive target genes.
Receptor-interacting protein (RIP) 140 interacts with several nuclear receptors, but its function in regulation of nuclear receptor action has been debated. Here we have examined the role of RIP140 in regulation of Steroidogenic factor-1 (SF-1)-dependent transcription. SF-1 interacts with RIP140 through its activation function-2 (AF-2) domain. Several domains of RIP140 interact directly with SF-1, but the carboxyl-terminal region containing 4 of its 9 LXXLL motifs showed the strongest SF-1 interaction. Coexpression of RIP140 and SF-1 in different cell types demonstrated that RIP140 acts as a potent corepressor of transcription from the SF-1 responsive cAMP regulatory sequence 2 (CRS2) element of the CYP17 gene and a variety of SF-1 responsive promoter genes. RIP140 also counteracted the stimulatory action of p160/SRC coactivators. The inhibitory effect of RIP140 was partially reversed by Trichostatin A, suggesting a role of histone deacetylase (HDAC) activity in RIP140-mediated repression of SF-1. Quantitation of endogenous coregulator mRNA levels revealed cell type specific differences that could affect the repressor action by overexpressed RIP140.
Mellgren
Gunnar
G
Department of Clinical Biochemistry, The Hormone Laboratory, Haukeland University Hospital, University of Bergen, N-5021 Bergen, Norway. gunnar.mellgren@med.uib.no
Børud
Bente
B
Hoang
Tuyen
T
Yri
Olav Erich
OE
Fladeby
Cathrine
C
Lien
Ernst Asbjørn
EA
Lund
Johan
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051717:Fushi Tarazu Transcription Factors; D005809:Genes, Regulator; D006655:Histone Deacetylases / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000078723:Nuclear Receptor Interacting Protein 1; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D012333:RNA, Messenger; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D013254:Steroid 17-alpha-Hydroxylase; D006655:Histone Deacetylases