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A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
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Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated

Lan V Pham1, Hai-Jun Zhou, Yen-Chiu Lin-Lee

  • 1Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

The Journal of Biological Chemistry
|December 21, 2007
PubMed

Insights

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is found in the nucleus, where it represses c-Myb. This novel nuclear function of TRAF6 in B-lymphocytes may maintain cell homeostasis and immune surveillance.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a known cytoplasmic adaptor protein crucial for immune signaling pathways like TNF-R:NF-kappaB.
  • Previous research has primarily focused on TRAF6's cytoplasmic role, neglecting its potential functions in other cellular compartments.

Purpose of the Study:

  • To investigate the presence and function of TRAF6 in the nucleus of B lymphocytes.
  • To elucidate the novel nuclear mechanisms regulated by TRAF6.

Main Methods:

  • Immunofluorescence and cell fractionation to determine TRAF6 localization.
  • Chromatin immunoprecipitation cloning to identify nuclear TRAF6 DNA binding targets.
  • Co-immunoprecipitation and Western blotting to analyze protein interactions and modifications.

Main Results:

  • TRAF6 is localized in the nucleus of both normal and malignant B lymphocytes, independent of a classical nuclear localization signal.
  • Nuclear TRAF6 binds to the c-Myb promoter and interacts with histone deacetylase 1 (HDAC1).
  • TRAF6 is modified by small ubiquitin-related modifier-1 (SUMO-1) and represses c-Myb-mediated transactivation.

Conclusions:

  • TRAF6 exerts a novel nuclear repressor function on c-Myb in B lymphocytes.
  • This nuclear role of TRAF6 contributes to the regulation of c-Myb, potentially maintaining cell homeostasis and immune surveillance.

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