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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Mol Cell Biol 2003 Jan
PMID:Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins. 1248 68

Transcriptional regulation by nuclear hormone receptors (NRs) requires multiple coregulators that modulate chromatin structures by catalyzing a diverse array of posttranslational modifications of histones. Different combinations of these modifications yield dynamic functional outcomes, constituting an epigenetic histone code. This code is inscribed by histone-modifying enzymes and decoded by effector proteins that recognize specific covalent marks. One important modification associated with active chromatin structures is methylation of histone H3-lysine 4 (H3K4). Crucial roles for this modification in NR transactivation have been recently highlighted through our purification and subsequent characterization of a steady-state complex associated with ASC-2, a coactivator of NRs and other transcription factors. This complex, designated ASCOM for ASC-2 complex, contains H3K4-methyltransferase MLL3/HALR or its paralogue MLL4/ALR and represents the first Set1-like H3K4-methyltransferase complex to be reported in vertebrates. This review focuses on recent progress in our understanding of how ASCOM-MLL3 and ASCOM-MLL4 influence NR-mediated gene transcription and of their physiological function.
Prog Mol Biol Transl Sci 2009
PMID:Roles of histone H3-lysine 4 methyltransferase complexes in NR-mediated gene transcription. 2037 9

Low expression of myeloid/lymphoid or mixed-lineage leukemia 3 (MLL3) is reportedly associated with gastric cancer and tumor progression. The purpose of this study was to examine the expression of MLL3 in tissue samples of patients with gastric cancer and to analyze the relationship between MLL3 protein expression and clinical records. Using immunohistochemical staining and Kaplan-Meier analysis for MLL3 in gastric cancer patients, we found that low expression of MLL3 had a significant relationship with a low survival rate compared to positive MLL3 expression in the patients analyzed (P<0.05). Our data suggest that MLL3 expression plays a vital role in gastric cancer development, and that this protein is an important marker for the prognosis of gastric cancer.
Genet Mol Res 2014 Sep 12
PMID:Association of MLL3 expression with prognosis in gastric cancer. 2522 51