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DAXX in cancer: phenomena, processes, mechanisms and regulation

Iqbal Mahmud1, Daiqing Liao1

  • 1Department of Anatomy and Cell Biology, UF Health Cancer Center, University of Florida College of Medicine, 1333 Center Drive, Gainesville, FL 32610-0235, USA.

Nucleic Acids Research
|July 28, 2019
PubMed

Insights

The protein DAXX, often overexpressed in cancer, drives tumor growth and treatment resistance. Understanding its structure and interactions is key to developing new cancer therapies.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Structural Biology

Background:

  • DAXX (Death-Domain Associated Protein) exhibits diverse biological roles.
  • Overexpression of DAXX is prevalent in various cancers, correlating with tumorigenesis, progression, and resistance to therapy.

Purpose of the Study:

  • To elucidate the complex biological functions of DAXX.
  • To understand how DAXX's structure facilitates its roles in oncogenesis and regulation.
  • To summarize current knowledge on DAXX's mechanisms in cancer promotion.

Main Methods:

  • Structural analysis of DAXX's modular domains (N-terminal helical bundle, H3.3/H4 interaction region, SUMO-interacting motifs).
  • Investigation of DAXX's interactions with transcription factors, epigenetic modifiers, and chromatin remodelers.
  • Analysis of DAXX's role in H3.3 deposition, DNA repair, viral infection, apoptosis, and cell signaling.
  • Examination of posttranslational modifications and SPOP-mediated degradation regulating DAXX activity.

Main Results:

  • DAXX's modular structure supports its diverse functions, including H3.3 chaperoning and binding to key regulatory proteins.
  • DAXX modulates transcription, DNA repair, and viral infection through interactions with chromatin and epigenetic machinery.
  • DAXX's activity is tightly regulated by posttranslational modifications and degradation pathways, such as SPOP-mediated degradation.

Conclusions:

  • DAXX's structural features are critical for its multifaceted biological activities.
  • DAXX plays a significant role in promoting oncogenesis through various molecular mechanisms.
  • Targeting DAXX or its regulatory pathways presents a potential strategy for cancer treatment.

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