Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors.
Small ubiquitin-like modifier (SUMO) modification has emerged as an important posttranslational control of protein functions. Daxx, a transcriptional corepressor, was reported to repress the transcriptional potential of several transcription factors and target to PML oncogenic domains (PODs) via SUMO-dependent interactions. The mechanism by which Daxx binds to sumoylated factors mediating ... transcriptional and subnuclear compartmental regulation remains unclear. Here, we define a SUMO-interacting motif (SIM) within Daxx and show it to be crucial for targeting Daxx to PODs and for transrepression of several sumoylated transcription factors, including glucocorticoid receptor (GR). In addition, the capability of Daxx SIM to bind SUMO also controls Daxx sumoylation. We further demonstrate that arsenic trioxide-induced sumoylation of PML correlates with a change of endogenous Daxx partitioning from GR-regulated gene promoter to PODs and a relief of Daxx repression on GR target gene expression. Our results provide mechanistic insights into Daxx in SUMO-dependent transcriptional control and subnuclear compartmentalization.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Amino Acid Sequence, Animals, Arsenicals, COS Cells, Carrier Proteins, Cell Nucleus, Cercopithecus aethiops, Dexamethasone, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Oxides, Protein Binding, Protein Structure, Tertiary, Protein Transport, Receptors, Glucocorticoid, Repressor Proteins, Small Ubiquitin-Related Modifier Proteins, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Amino Acid Sequence, Animals, Arsenicals, COS Cells, Carrier Proteins, Cell Nucleus, Cercopithecus aethiops, Dexamethasone, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Oxides, Protein Binding, Protein Structure, Tertiary, Protein Transport, Receptors, Glucocorticoid, Repressor Proteins, Small Ubiquitin-Related Modifier Proteins, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins
Mol. Cell
Date: Nov. 03, 2006
PubMed ID: 17081986
View in: Pubmed Google Scholar
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- Interactions 17
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