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Characterization of nuclear localization and SUMOylation of the ATBF1 transcription factor in epithelial cells

Xiaodong Sun1, Jie Li1, Frederick N Dong1

  • 1Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, United States of America.

Plos One
|March 22, 2014
PubMed

Insights

ATBF1/ZFHX3, a nuclear transcription factor, forms nuclear dots and is SUMOylated. Its nuclear localization signal (NLS) and SUMOylation sites were identified, revealing interactions with PML NBs and SUMO1 regulation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • ATBF1/ZFHX3 is a crucial transcription factor involved in development and tumorigenesis.
  • Mislocalization of ATBF1 from the nucleus to the cytoplasm is observed in cancer cells, but the mechanism is unclear.
  • Understanding ATBF1's localization and post-translational modifications is key to its function.

Purpose of the Study:

  • To investigate the mechanism of ATBF1 nuclear localization.
  • To identify the nuclear localization signal (NLS) of ATBF1.
  • To explore the SUMOylation of ATBF1 and its relationship with nuclear bodies and SUMO1.

Main Methods:

  • Analysis of ectopic ATBF1 expression and localization in the nucleus.
  • Identification of a specific 3-amino acid motif (KRK2615-2617) as the ATBF1 NLS.
  • Investigation of ATBF1's association with promyelocytic leukemia (PML) nuclear bodies (NBs) and SUMO1.
  • Identification of ATBF1 SUMOylation sites (K2349, K2806, K3258) and the role of PIAS3.

Main Results:

  • Ectopically expressed ATBF1 forms nuclear body (NB)-like dots, some associating with PML NBs.
  • A KRK motif (2615-2617) was identified as the NLS for ATBF1.
  • ATBF1 sequesters nuclear SUMO1 into its dots and is itself SUMOylated at multiple lysine residues.
  • PIAS3, an E3 SUMO ligase, diminishes ATBF1 SUMOylation and prevents ATBF1-SUMO1 co-localization.

Conclusions:

  • Nuclear localization and SUMOylation are critical for ATBF1's transcription factor activity.
  • ATBF1 interacts with PML NBs and influences SUMO1 localization, suggesting a role in regulating protein SUMOylation.
  • These findings provide insights into ATBF1 function in biological processes and cancer.

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