Characterization of Aes nuclear foci in colorectal cancer cells

J Biochem. 2016 Jan;159(1):133-40. doi: 10.1093/jb/mvv077. Epub 2015 Jul 29.


Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling.

Keywords: Notch signalling; colorectal cancer; heat shock protein; nuclear matrix; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Cell Nucleus / metabolism*
  • Cell Nucleus / ultrastructure
  • Co-Repressor Proteins
  • Colorectal Neoplasms / metabolism*
  • Cytokinesis
  • HCT116 Cells
  • HEK293 Cells
  • HSC70 Heat-Shock Proteins / antagonists & inhibitors
  • HSC70 Heat-Shock Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Microscopy, Immunoelectron
  • Mitosis
  • Purine Nucleosides / pharmacology
  • Receptors, Notch / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Time-Lapse Imaging


  • Co-Repressor Proteins
  • HSC70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Purine Nucleosides
  • Receptors, Notch
  • Repressor Proteins
  • TLE1 protein, human
  • TLE5 protein, human
  • VER 155008
  • Adenosine Triphosphatases