Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2002-10-15
pubmed:abstractText
The human P450scc gene is regulated by the tissue-specific orphan nuclear receptor, steroidogenic factor-1 (SF-1), which plays a key role in several physiologic processes including steroid synthesis, adrenal and gonadal development, and sexual differentiation. Several studies have demonstrated the interaction of SF-1 with different proteins. However, it is clear that additional factors not yet identified are involved with SF-1 to regulate different target genes. Recently, it was demonstrated that a novel transcriptional regulating protein of 132 kDa (TReP-132) regulates expression of the human P450scc gene. The overexpression of TReP-132 in adrenal cells increases the production of pregnenolone, which is associated with the activation of P450scc gene expression. Considering the colocalization of TReP-132 and SF-1 in steroidogenic tissues such as the adrenal and testis, and the presence of two putative LXXLL motifs in TReP-132 that can potentially interact with SF-1, the relationship between these two factors on the P450scc gene promoter was determined. The coexpression of SF-1 and TReP-132 in adrenal NCI-H295 cells cooperates to increase promoter activity. Pull-down experiments demonstrated the interaction between TReP-132 and SF-1, and this was further confirmed in intact cells by coimmunoprecipitation/Western blot and two-hybrid analyses. Deletions and mutations of the TReP-132 cDNA sequence demonstrate that SF-1 interaction requires the LXXLL motif found at the amino-terminal region of the protein. Also, the "proximal activation domain" and the "AF-2 hexamer" motif of SF-1 are involved in interaction with TReP-132. Consistent with previous studies showing interaction between CBP/p300 and SF-1 or TReP-132, the coexpression of these three proteins results in a synergistic effect on P450scc gene promoter activity. Taken together the results in this study identify a novel function of TReP-132 as a partner in a complex with SF-1 and CBP/p300 to regulate gene transcription involved in steroidogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol Side-Chain Cleavage..., http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Ep300 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Fushi Tarazu Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase, http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/NR5A1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Pregnenolone, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Steroidogenic Factor 1, http://linkedlifedata.com/resource/pubmed/chemical/TRERF1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic factor 1, mouse
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39144-55
pubmed:dateRevised
2009-8-12
pubmed:meshHeading
pubmed-meshheading:12101186-Adrenal Gland Neoplasms, pubmed-meshheading:12101186-Adrenal Glands, pubmed-meshheading:12101186-Amino Acid Motifs, pubmed-meshheading:12101186-Animals, pubmed-meshheading:12101186-Blotting, Western, pubmed-meshheading:12101186-Cholesterol Side-Chain Cleavage Enzyme, pubmed-meshheading:12101186-Chromatography, High Pressure Liquid, pubmed-meshheading:12101186-DNA, Complementary, pubmed-meshheading:12101186-DNA-Binding Proteins, pubmed-meshheading:12101186-E1A-Associated p300 Protein, pubmed-meshheading:12101186-Fushi Tarazu Transcription Factors, pubmed-meshheading:12101186-Glutathione Transferase, pubmed-meshheading:12101186-Homeodomain Proteins, pubmed-meshheading:12101186-Humans, pubmed-meshheading:12101186-Luciferases, pubmed-meshheading:12101186-Mice, pubmed-meshheading:12101186-Models, Genetic, pubmed-meshheading:12101186-Nuclear Proteins, pubmed-meshheading:12101186-Plasmids, pubmed-meshheading:12101186-Precipitin Tests, pubmed-meshheading:12101186-Pregnenolone, pubmed-meshheading:12101186-Promoter Regions, Genetic, pubmed-meshheading:12101186-Protein Binding, pubmed-meshheading:12101186-Protein Structure, Tertiary, pubmed-meshheading:12101186-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:12101186-Steroidogenic Factor 1, pubmed-meshheading:12101186-Time Factors, pubmed-meshheading:12101186-Trans-Activators, pubmed-meshheading:12101186-Transcription, Genetic, pubmed-meshheading:12101186-Transcription Factors, pubmed-meshheading:12101186-Transfection, pubmed-meshheading:12101186-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells.
pubmed:affiliation
Oncology and Molecular Endocrinology Research Center, Laval University, Québec GIK 7P4, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't