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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression

Gemma Ferrer-Mayorga1, Silvia Alvarez-Díaz1, Noelia Valle1

  • 1From the Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, E-28029 Madrid.

The Journal of Biological Chemistry
|September 15, 2015
PubMed

Insights

Cystatin D, a protease inhibitor, unexpectedly acts within the cell nucleus. It influences gene expression and cytokine secretion, revealing a novel tumor suppressor role in colon carcinoma.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cystatin D is known as an inhibitor of cysteine proteases.
  • Previous studies suggested cystatin D possesses tumor suppressor activity in colon carcinoma, independent of protease inhibition.

Purpose of the Study:

  • To investigate the non-protease inhibitory functions of cystatin D.
  • To elucidate the nuclear role of cystatin D in colon carcinoma cells.

Main Methods:

  • Cellular localization studies to determine cystatin D's intracellular site.
  • Transcriptomic and quantitative proteomic analyses to assess gene and protein expression changes.
  • Cytokine array analysis to evaluate secreted factors.

Main Results:

  • Cystatin D was found in the nucleus at transcriptionally active chromatin sites.
  • Gene expression analysis revealed alterations in transcription factors like RUNX1, RUNX2, and MEF2C.
  • Proteomic analysis identified changes in proteins related to cell adhesion, cytoskeleton, and RNA processing.
  • Cystatin D reduced secretion of protumorigenic cytokines, including FGF-4 and TGF-B3.

Conclusions:

  • Cystatin D has a novel nuclear function in regulating gene transcription.
  • These nuclear activities contribute to its tumor suppressor effects in colon cancer.
  • Cystatin D's role extends beyond protease inhibition, impacting key cellular processes.
Keywords:
colon cancercysteine proteasecytokinegene expressionprotease inhibitor

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