Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors

Mol Cell. 2006 Nov 3;24(3):341-54. doi: 10.1016/j.molcel.2006.10.019.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Arsenic Trioxide
  • Arsenicals / pharmacology
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism*
  • Chlorocebus aethiops
  • Dexamethasone / pharmacology
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Molecular Chaperones
  • Molecular Sequence Data
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Oxides / pharmacology
  • Promyelocytic Leukemia Protein
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Receptors, Glucocorticoid / metabolism
  • Repressor Proteins / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Suppressor Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Arsenicals
  • Carrier Proteins
  • DAXX protein, human
  • Daxx protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oxides
  • Pml protein, mouse
  • Promyelocytic Leukemia Protein
  • Receptors, Glucocorticoid
  • Repressor Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Dexamethasone
  • Arsenic Trioxide