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Published on: October 10, 2017
Characterization of Aes nuclear foci in colorectal cancer cells
Yoshiro Itatani1, Masahiro Sonoshita2, Fumihiko Kakizaki2
1Department of Pharmacology and Department of Surgery, Graduate School of Medicine, Kyoto University, Yoshida Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan;
Abstract:
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.
Insights
Amino-terminal enhancer of split (Aes) nuclear foci in colorectal cancer dissolve during mitosis and reform post-cytokinesis. Heat shock cognate 70 (HSC70) is crucial for Aes focus formation and Notch signaling inhibition.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Amino-terminal enhancer of split (Aes) is a metastasis suppressor in colorectal cancer (CRC) that inhibits Notch signaling.
- Aes forms nuclear foci with TLE1, but the dynamics and function of these structures are poorly understood.
Purpose of the Study:
- To investigate the structural dynamics and essential components of Aes nuclear foci in colorectal cancer cells.
- To elucidate the role of heat shock cognate 70 (HSC70) in Aes focus formation and its implications for Notch signaling.
Main Methods:
- Electron microscopy to characterize Aes nuclear foci structure.
- Time-lapse cinematography to observe Aes foci behavior during the cell cycle.
- Pharmacological inhibition of HSC70 ATPase activity using VER155008.
Main Results:
- Aes nuclear foci are amorphous structures lacking a surrounding membrane.
- Aes foci dissolve during mitosis and reassemble after cytokinesis.
- HSC70 is essential for Aes focus formation, and its inhibition reduces focus assembly.
Conclusions:
- Aes nuclear foci exhibit dynamic behavior throughout the cell cycle, dependent on HSC70.
- Understanding Aes foci dynamics and HSC70 interaction provides insights into Aes-mediated Notch signaling inhibition in CRC.
