Cloning and characterization of GETS-1, a goldfish Ets family member that functions as a transcriptional repressor in muscle

• Published in: Biochemical journal Vol. 335 ( Pt 2); no. 2; pp. 267 - 275
• Main Authors: Goldman, D, Sapru, M K, Stewart, S, Plotkin, J, Libermann, T A, Wasylyk, B, Guan, K
• Format: Journal Article
• Language: English
• Published: England Portland Press 15.10.1998
• Subjects: Amino Acid Sequence; Animals; Biochemistry, Molecular Biology; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cells, Cultured; Cloning, Molecular; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epidermal Growth Factor - pharmacology; ets-Domain Protein Elk-4; Gene Expression Regulation; Goldfish - genetics; Life Sciences; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Molecular Sequence Data; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Phosphorylation; Promoter Regions, Genetic; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ets; ras Proteins - genetics; ras Proteins - metabolism; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; Repressor Proteins - drug effects; Repressor Proteins - genetics; Repressor Proteins - metabolism; Retina; Sequence Homology, Amino Acid; Tetradecanoylphorbol Acetate - pharmacology; Transcription Factors - drug effects; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3350267

An Ets transcription factor family member, GETS-1, was cloned from a goldfish retina cDNA library. GETS-1 contains a conserved Ets DNA-binding domain at its N-terminus and is most similar to ternary complex factor (TCF) serum-response-factor protein-1a (SAP-1a). GETS-1 is expressed in many tissues, but is enriched in retina and brain. As with the TCFs SAP-1a and ets-related protein (ERP), overexpression of the GETS-1 promoter suppresses nicotinic acetylcholine receptor epsilon-subunit gene expression in cultured muscle cells. A consensus Ets binding site sequence in the promoter of the epsilon-subunit gene is required for GETS-1-mediated repression. GETS-1 repressor activity is abrogated by overexpression of an activated Ras/mitogen-activated protein kinase (MAP kinase) or by mutation of Ser-405, a MAP kinase phosphorylation site in GETS-1. Fusion proteins created between GETS-1 and the Gal4 DNA-binding domain show that, like other TCFs, GETS-1 contains a C-terminal activation domain that is activated by a Ras/MAP kinase signalling cascade. Interestingly, mutation of Ser-405 located within this activation domain abrogated transcriptional activation of the fusion protein.