Linked Life Data

18245227

Source:http://linkedlifedata.com/resource/pubmed/id/18245227

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-3-3
pubmed:abstractText
Sterol regulatory element-binding protein-1c (SREBP-1c) is a basic helix-loop-helix transcription factor that plays an important role in lipid homeostasis. Here, we show that SREBP-1c regulates androgen receptor (AR) transactivation through direct interaction with AR and represses androgen-dependent growth of prostatic cells. Transient transfection studies show that SREBP-1c specifically inhibits the transactivation of AR. Chromatin immunoprecipitation assays reveal that SREBP-1c is recruited with AR onto the endogenous AR target promoter. Moreover, adenovirus-mediated overexpression of SREBP-1c decreases the mRNA level of the prostate-specific antigen gene, an endogenous target gene of AR, supporting SREBP-1c modulation of AR transactivation. In vivo and in vitro protein interaction assays show that SREBP-1c directly interacts with AR through the activation function-1 domain of AR. In addition, transfection studies and glutathione S-transferase pull-down competition experiments reveal that the SREBP-1c-mediated repression of AR transactivation is accomplished through competition with certain AR coactivators for AR interaction. The SREBP-1c-mediated inhibition of AR transactivation also involves the recruitment of histone deacetylase 1. Finally, adenovirus-mediated overexpression of SREBP-1c inhibits androgen-induced proliferation of prostatic cells in vitro and in vivo, and small interfering RNA-mediated down-regulation of SREBP-1 enhances androgen-induced proliferation of prostatic cells as well as the transactivation of AR. Taken together, these results suggest that SREBP-1c acts as an AR corepressor and may play an important role in the regulation of AR-dependent prostatic cell growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
314-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18245227-Androgens, pubmed-meshheading:18245227-Animals, pubmed-meshheading:18245227-Cell Line, Tumor, pubmed-meshheading:18245227-Cell Proliferation, pubmed-meshheading:18245227-Histone Deacetylase 1, pubmed-meshheading:18245227-Histone Deacetylases, pubmed-meshheading:18245227-Male, pubmed-meshheading:18245227-Mice, pubmed-meshheading:18245227-Promoter Regions, Genetic, pubmed-meshheading:18245227-Prostate, pubmed-meshheading:18245227-Protein Binding, pubmed-meshheading:18245227-Receptors, Androgen, pubmed-meshheading:18245227-Repressor Proteins, pubmed-meshheading:18245227-Sterol Regulatory Element Binding Protein 1, pubmed-meshheading:18245227-Transcription, Genetic, pubmed-meshheading:18245227-Transcriptional Activation, pubmed-meshheading:18245227-Xenograft Model Antitumor Assays
pubmed:year
2008
pubmed:articleTitle
Sterol regulatory element-binding protein-1c represses the transactivation of androgen receptor and androgen-dependent growth of prostatic cells.
pubmed:affiliation
Hormone Research Center, Chonnam National University, Gwangju, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't