Sumoylation of TCF21 downregulates the transcriptional activity of estrogen receptor-alpha

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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

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Xiang Ao1, Shujing Li1, Zhaowei Xu1

  • 1School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People's Republic of China.

Oncotarget
|March 31, 2016
PubMed

Insights

Transcription factor 21 (TCF21) represses estrogen receptor-α (ERα) activity in breast cancer. TCF21 sumoylation enhances this repression by increasing HDAC1/2 recruitment, inhibiting cancer cell growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Aberrant estrogen receptor-α (ERα) signaling drives breast cancer development.
  • The precise molecular mechanisms regulating ERα in breast cancer remain incompletely understood.

Purpose of the Study:

  • To investigate the interaction between transcription factor 21 (TCF21) and ERα.
  • To elucidate the role of TCF21 post-translational modifications, specifically sumoylation, in ERα regulation.
  • To determine the impact of TCF21 sumoylation on breast cancer cell growth.

Main Methods:

  • Co-immunoprecipitation assays to assess protein interactions.
  • Western blotting to detect sumoylation and protein stability.
  • Site-directed mutagenesis to identify sumoylation sites.
  • Chromatin immunoprecipitation to analyze protein recruitment to promoters.
  • Cell cycle analysis and cell proliferation assays.

Main Results:

  • TCF21 interacts with ERα and represses its transcriptional activity in a manner dependent on histone deacetylases (HDACs).
  • TCF21 undergoes sumoylation at lysine 24 (K24) by SUMO1, a process reversible by SENP1.
  • Sumoylation stabilizes TCF21, enhances its interaction with HDAC1/2, and promotes ERα repression via increased HDAC1/2 recruitment to the pS2 promoter.
  • Sumoylated TCF21 inhibits ERα-positive breast cancer cell growth and reduces the proportion of S-phase cells.

Conclusions:

  • TCF21 functions as a negative regulator of ERα transcriptional activity in breast cancer.
  • TCF21 sumoylation enhances its repressive function by facilitating HDAC recruitment, thereby inhibiting breast cancer cell proliferation.
  • Targeting TCF21 sumoylation represents a potential therapeutic strategy for ERα-positive breast cancer.
Keywords:
ERαTCF21proliferationsumoylationtranscriptional activity

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