Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.
Iourgenko V,
Zhang W,
Mickanin C,
Daly I,
Jiang C,
Hexham JM,
Orth AP,
Miraglia L,
Meltzer J,
Garza D,
Chirn GW,
McWhinnie E,
Cohen D,
Skelton J,
Terry R,
Yu Y,
Bodian D,
Buxton FP,
Zhu J,
Song C,
Labow MA.
Department of Functional Genomics, Novartis Institute for Biomedical Research, 100 Technology Square, Cambridge, MA 02139, USA.
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.
PMID: 14506290 [PubMed - indexed for MEDLINE]
PMCID: PMC218727