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Related Experiment Videos

C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs.

Madeleine Grooteclaes1, Quinn Deveraux, Jeffrey Hildebrand

  • 1The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 5, 2003
PubMed
Summary

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C-terminal-binding protein (CtBP) represses epithelial genes, enabling cancer cell transitions. CtBP also regulates apoptosis sensitivity, establishing key roles in cancer progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Carcinoma genesis involves epithelial-to-mesenchymal transitions (EMTs) and apoptosis resistance.
  • The role of C-terminal-binding protein (CtBP) in coordinating these processes was unclear.
  • Previous studies suggested CtBP might repress epithelial cell adhesion and proapoptotic genes.

Purpose of the Study:

  • To investigate the functional roles of CtBP in regulating epithelial genes and apoptosis.
  • To determine if CtBP controls epithelial-to-mesenchymal transitions and apoptosis resistance coordinately.
  • To elucidate the mechanism of CtBP's function, including the role of histidine-315.

Main Methods:

  • CtBP knockout and rescue experiments in mouse embryo fibroblasts.

Related Experiment Videos

  • Microarray analysis to identify CtBP-regulated genes.
  • Functional assays to assess apoptosis sensitivity and gene repression activities.

    • Main Results:

    • CtBP-knockout cells exhibited hypersensitivity to apoptosis.
    • Microarray analysis confirmed CtBP regulates many epithelial-specific and proapoptotic genes.
    • CtBP's apoptosis and repression activities did not require histidine-315, indicating dehydrogenase activity is not essential.

    Conclusions:

    • CtBP plays a dual role: corepressing epithelial genes to permit EMTs and modulating apoptosis thresholds.
    • These functions establish CtBP as a key regulator in cancer cell progression.
    • CtBP's activity is independent of its proposed dehydrogenase function.