rdf:type |
|
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0033684,
umls-concept:C0040649,
umls-concept:C0086418,
umls-concept:C0521428,
umls-concept:C1413855,
umls-concept:C1425411,
umls-concept:C1704675,
umls-concept:C1705389,
umls-concept:C1707172,
umls-concept:C1998811,
umls-concept:C2349975
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pubmed:issue |
42
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pubmed:dateCreated |
2002-10-15
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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.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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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
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
39144-55
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pubmed:dateRevised |
2009-8-12
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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
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pubmed:year |
2002
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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.
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pubmed:affiliation |
Oncology and Molecular Endocrinology Research Center, Laval University, Québec GIK 7P4, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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