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Proc Natl Acad Sci U S A ; 100(21): 12147-52, 2003 Oct 14.
Article in English | MEDLINE | ID: mdl-14506290

ABSTRACT

This report describes an unbiased method for systematically determining gene function in mammalian cells. A total of 20,704 predicted human full-length cDNAs were tested for induction of the IL-8 promoter. A number of genes, including those for cytokines, receptors, adapters, kinases, and transcription factors, were identified that induced the IL-8 promoter through known regulatory sites. Proteins that acted through a cooperative interaction between an AP-1 and an unrecognized cAMP response element (CRE)-like site were also identified. A protein, termed transducer of regulated cAMP response element-binding protein (CREB) (TORC1), was identified that activated expression through the variant CRE and consensus CRE sites. TORC1 potently induced known CREB1 target genes, bound CREB1, and activated expression through a potent transcription activation domain. A functional Drosophila TORC gene was also identified. Thus, TORCs represent a family of highly conserved CREB coactivators that may control the potency and specificity of CRE-mediated responses.


Subject(s)
Cyclic AMP Response Element-Binding Protein/metabolism , Trans-Activators/genetics , Trans-Activators/metabolism , Amino Acid Sequence , Cell Line , DNA, Complementary/genetics , Gene Expression Profiling , Genome, Human , HeLa Cells , Humans , Interleukin-8/genetics , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , Promoter Regions, Genetic , Sequence Homology, Amino Acid , Transcription Factors/metabolism , Transfection
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