Iourgenko, V., Zhang, W., Mickanin, C., Daly, I., Jiang, C., Hexham, J.M., Orth, A.P., Miraglia, L., Meltzer, J., Garza, D., Chrin, G.W., McWhinnie, E., Cohen, D., Skelton, J., Terry, R., Yu, Y., Bodian, D., Buxton, F.P., Zhu, J., Song, C., Labow, M.A. (2003). Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.  Proc. Natl. Acad. Sci. U.S.A. 100(21): 12147--12152.

FBrf0173108

Research paper

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.

PMC218727 (PMC) (EuropePMC)