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SP1 and RARα regulate AGAP2 expression in cancer

Yegor Doush1, Arif A Surani1, Amaia Navarro-Corcuera1,2

  • 1College of Science and Technology, Nottingham Trent University, Nottingham, UK.

Scientific Reports
|January 25, 2019
PubMed

Insights

Researchers identified SP1 as a key factor regulating the proto-oncogene AGAP2 (Arf GAP with GTP-binding protein-like domain, Ankyrin repeat and PH domain 2) expression. Treatments with ATRA and curcumin also modulated AGAP2 levels in cancer cells.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • AGAP2 (Arf GAP with GTP-binding protein-like domain, Ankyrin repeat and PH domain 2) isoform 2 is a proto-oncogene with poorly understood gene expression regulation.
  • Understanding AGAP2 regulation is crucial for cancers where it is overexpressed.

Purpose of the Study:

  • To investigate the regulatory mechanisms of AGAP2 gene expression.
  • To identify transcription factors and signaling pathways involved in AGAP2 regulation.

Main Methods:

  • Cloning and characterization of the AGAP2 proximal promoter using reporter assays.
  • SP1 silencing experiments in KU812 (myeloid leukemia) and DU145 (prostate cancer) cell lines.
  • Chromatin immunoprecipitation (ChIP) assays to identify proteins bound to the AGAP2 promoter.

Main Results:

  • SP1 was identified as a transcription factor essential for AGAP2 expression in both cancer cell lines.
  • Silencing SP1 significantly decreased AGAP2 protein levels.
  • All-trans retinoic acid (ATRA) treatment increased AGAP2 protein levels, while curcumin reduced this ATRA-mediated increase.
  • ChIP studies confirmed the presence of RARα, RXRα, and PCAF at the AGAP2 promoter.

Conclusions:

  • This study elucidates novel aspects of AGAP2 expression regulation, involving SP1, ATRA, and curcumin.
  • The findings offer potential therapeutic insights for cancers associated with AGAP2 overexpression.

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