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We report here the identification of a novel cofactor, ACTR, that directly binds nuclear receptors and stimulates their transcriptional activities in a hormone-dependent fashion. ACTR also recruits two other nuclear factors, CBP and P/CAF, and thus plays a central role in creating a multisubunit coactivator complex. In addition, and unexpectedly, we show(More)
Thyroid hormones (THs) are essential for fetal and post-natal nervous system development and also play an important role in the maintenance of adult brain function. Of the two major THs, T4 (3,5,3',5'-tetraiodo-l-thyronine) is classically viewed as an pro-hormone that must be converted to T3 (3,5,3'-tri-iodo-l-thyronine) via tissue-level deiodinases for(More)
Thyroid hormone receptors (TRs) are hormone-regulated transcription factors that control multiple aspects of normal physiology and development. Mutations in TRs have been identified at high frequency in certain cancers, including human hepatocellular carcinomas (HCCs). The majority of HCC-TR mutants bear lesions within their DNA recognition domains, and we(More)
The SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptors) corepressor mediates gene repression by nuclear receptors and other transcriptional factors. The SMRT protein serves as a key nucleating core that organizes the assembly of a larger corepressor complex. We report here that SMRT interacts with itself to form a protein dimer, and that(More)
The SMRT and NCoR corepressors bind to, and mediate transcriptional repression by, many nuclear receptors. Both SMRT and NCoR are expressed by alternative mRNA splicing, generating a series of structurally and functionally distinct corepressor "variants". We report that a splice variant of SMRT, SMRTε, recognizes a restricted subset of nuclear receptors.(More)
Molecular and Cellular Biology offers three major programs: Biochemistry and Molecular Biology, Cell Biology, and Genetics and Genomics. The Biochemistry and Molecular Biology major introduces students to the chemistry of living organisms and the experimental techniques that are used to probe the structures and functions of biologically important molecules.(More)
The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is functionally implicated in their survival and proliferation. In the present study, we show that GATA-2 exists as an acetylated protein in immature precursor cells, KG1. GATA-2 was acetylated in vitro by p300 and GCN5. We have identified multiple acetylation sites(More)