Abstract
Daxx has been shown to play an essential role in type I IFN-alphabeta-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify how Daxx regulates B cell development, we examined Daxx interacting partners by yeast two-hybrid screening. DNA methyltransferase 1 (DNMT1)-associated protein (DMAP1) was identified and demonstrated to interact with Daxx. The interaction regions in both proteins were mapped, and the cellular localization of the interaction was examined. Both Daxx and DMAP1 formed a complex with DNMT1 and colocalized in the nucleus. DMAP1 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. Furthermore, Daxx protected protein degradation of DMAP1 in vivo. These results provide the novel molecular link between Daxx and DNMT1, which establishes a repressive transcription complex in the nucleus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Apoptosis / genetics
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B-Lymphocytes / cytology
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B-Lymphocytes / enzymology
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B-Lymphocytes / metabolism
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COS Cells
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Carrier Proteins / chemistry*
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Line, Tumor
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Co-Repressor Proteins
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Cysteine Endopeptidases / metabolism
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases / chemistry*
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DNA (Cytosine-5-)-Methyltransferases / genetics
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DNA (Cytosine-5-)-Methyltransferases / physiology*
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Drug Synergism
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins*
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Mice
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Molecular Chaperones
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Multienzyme Complexes / antagonists & inhibitors
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Multienzyme Complexes / metabolism
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Proteasome Endopeptidase Complex
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Protein Interaction Mapping
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Receptors, Glucocorticoid / antagonists & inhibitors
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Receptors, Glucocorticoid / physiology
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Repressor Proteins / chemistry*
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Stem Cells / cytology
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Stem Cells / enzymology
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Stem Cells / metabolism
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / physiology
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Co-Repressor Proteins
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DAXX protein, human
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DMAP1 protein, human
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Daxx protein, mouse
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Dmap1 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Molecular Chaperones
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Multienzyme Complexes
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Nuclear Proteins
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Receptors, Glucocorticoid
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Repressor Proteins
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Trans-Activators
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNMT1 protein, human
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Dnmt1 protein, mouse
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex