DAXX in cancer: phenomena, processes, mechanisms and regulation

Nucleic Acids Res. 2019 Sep 5;47(15):7734-7752. doi: 10.1093/nar/gkz634.


DAXX displays complex biological functions. Remarkably, DAXX overexpression is a common feature in diverse cancers, which correlates with tumorigenesis, disease progression and treatment resistance. Structurally, DAXX is modular with an N-terminal helical bundle, a docking site for many DAXX interactors (e.g. p53 and ATRX). DAXX's central region folds with the H3.3/H4 dimer, providing a H3.3-specific chaperoning function. DAXX has two functionally critical SUMO-interacting motifs. These modules are connected by disordered regions. DAXX's structural features provide a framework for deciphering how DAXX mechanistically imparts its functions and how its activity is regulated. DAXX modulates transcription through binding to transcription factors, epigenetic modifiers, and chromatin remodelers. DAXX's localization in the PML nuclear bodies also plays roles in transcriptional regulation. DAXX-regulated genes are likely important effectors of its biological functions. Deposition of H3.3 and its interactions with epigenetic modifiers are likely key events for DAXX to regulate transcription, DNA repair, and viral infection. Interactions between DAXX and its partners directly impact apoptosis and cell signaling. DAXX's activity is regulated by posttranslational modifications and ubiquitin-dependent degradation. Notably, the tumor suppressor SPOP promotes DAXX degradation in phase-separated droplets. We summarize here our current understanding of DAXX's complex functions with a focus on how it promotes oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Line, Tumor
  • Chromatin / chemistry
  • Co-Repressor Proteins
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Molecular Chaperones
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational*
  • Signal Transduction
  • Sumoylation
  • Transcription, Genetic
  • Ubiquitination


  • Adaptor Proteins, Signal Transducing
  • Chromatin
  • Co-Repressor Proteins
  • DAXX protein, human
  • Molecular Chaperones
  • Neoplasm Proteins
  • Nuclear Proteins