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SERBP1 Is a Component of the Liver Receptor Homologue-1 Transcriptional Complex

Yelenis Mari1, Graham M West1, Catherina Scharager-Tapia1

  • 1Department of Molecular Therapeutics, ‡Mass Spectrometry & Proteomics Core, and §Informatics Core, The Scripps Research Institute , Jupiter, Florida 33458, United States.

Journal of Proteome Research
|September 24, 2015
PubMed

Insights

Liver receptor homologue-1 (LRH1) regulates gene transcription in cancer. Researchers identified SERBP1 and ILF3 as LRH1 partners, with LRH1 inhibiting SERBP1 expression, offering potential therapeutic targets.

Area of Science:

  • Molecular biology
  • Cancer research
  • Nuclear receptor signaling

Background:

  • Liver receptor homologue-1 (LRH1) is an orphan nuclear receptor implicated in cancer-related pathways.
  • Understanding LRH1's transcriptional complex is crucial for elucidating its role in cancer and endogenous regulation.

Purpose of the Study:

  • To identify co-regulators of LRH1 using proteomic approaches.
  • To investigate the interaction between LRH1, SERBP1, and ILF3.
  • To explore the functional consequences of LRH1 binding on SERBP1 transcription.

Main Methods:

  • Sub-cellular enrichment and nuclear fractionation followed by mass spectrometry (MS).
  • Western blot and MS/MS analysis to identify interacting partners.
  • siRNA-mediated knockdown and overexpression studies.
  • Promoter:reporter assays to assess transcriptional regulation.

Main Results:

  • SERBP1 and ILF3 were identified as LRH1 interacting partners.
  • LRH1 knockdown increased SERBP1 expression; LRH1 overexpression decreased SERBP1 mRNA.
  • LRH1 binding to the SERBP1 promoter inhibited reporter gene expression, suppressing transcription.

Conclusions:

  • The study identifies SERBP1 and ILF3 as components of the LRH1 transcriptional complex.
  • LRH1 directly represses SERBP1 transcription.
  • These findings provide insights into LRH1 signaling in cancer and suggest potential therapeutic targets.
Keywords:
SERPINE1 mRNA binding protein-1 (SERBP1)interleukin enhancer binding factor-3 (ILF3)liver receptor homologue-1 (LRH1; NR5A2)nuclear receptorperoxisome proliferator-activated receptor γ co-activator-1α (PGC1α)protein arginine methyltransferase 1 (PRMT1)

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