Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins.
Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. These include activating signal cointegrator 2 (ASC-2), a recently isolated transcriptional coactivator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors and numerous other transcription factors. In this report, we ... show that ASC-2 belongs to a steady-state complex of approximately 2 MDa (ASC-2 complex [ASCOM]) in HeLa nuclei. ASCOM contains retinoblastoma-binding protein RBQ-3, alpha/beta-tubulins, and trithorax group proteins ALR-1, ALR-2, HALR, and ASH2. In particular, ALR-1/2 and HALR contain a highly conserved 130- to 140-amino-acid motif termed the SET domain, which was recently implicated in histone H3 lysine-specific methylation activities. Indeed, recombinant ALR-1, HALR, and immunopurified ASCOM exhibit very weak but specific H3-lysine 4 methylation activities in vitro, and transactivation by retinoic acid receptor appears to involve ligand-dependent recruitment of ASCOM and subsequent transient H3-lysine 4 methylation of the promoter region in vivo. Thus, ASCOM may represent a distinct coactivator complex of nuclear receptors. Further characterization of ASCOM will lead to a better understanding of how nuclear receptors and other transcription factors mediate transcriptional activation.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Carrier Proteins, Cation Transport Proteins, Cell Nucleus, DNA-Binding Proteins, Drosophila Proteins, Hela Cells, Histones, Humans, Intracellular Signaling Peptides and Proteins, Lysine, Macromolecular Substances, Methylation, Molecular Sequence Data, Nuclear Proteins, Nuclear Receptor Coactivators, Receptors, Retinoic Acid, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Transcription Factors, Tubulin
Amino Acid Motifs, Amino Acid Sequence, Animals, Carrier Proteins, Cation Transport Proteins, Cell Nucleus, DNA-Binding Proteins, Drosophila Proteins, Hela Cells, Histones, Humans, Intracellular Signaling Peptides and Proteins, Lysine, Macromolecular Substances, Methylation, Molecular Sequence Data, Nuclear Proteins, Nuclear Receptor Coactivators, Receptors, Retinoic Acid, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Transcription Factors, Tubulin
Mol. Cell. Biol.
Date: Jan. 01, 2003
PubMed ID: 12482968
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