April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
EGF- and UV Stress-regulated CTCF Function Through Canonical And Non-canonical NF-B Pathways
Author Affiliations & Notes
  • Yumei Wang
    Department of Medicine, David Geffen School of Medicine, UCLA, Torrance, California
  • Luo Lu
    Department of Medicine, David Geffen School of Medicine, UCLA, Torrance, California
  • Footnotes
    Commercial Relationships  Yumei Wang, None; Luo Lu, None
  • Footnotes
    Support  NIH-EY015281
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 313. doi:
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      Yumei Wang, Luo Lu; EGF- and UV Stress-regulated CTCF Function Through Canonical And Non-canonical NF-B Pathways. Invest. Ophthalmol. Vis. Sci. 2011;52(14):313.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : CCCTC factor (CTCF), an epigenetic factor, controls important gene expressions. The purpose of the present study is to investigate the mechanism(s) that involves in EGF- and UV stress-induced regulation of CTCF through the canonical and non-canonical NF-ΚB pathways to affect human corneal epithelial (HCE) fate.

Methods: : EGF (20 ng/ml) and/or UV irradiation (245 nm at 42 µJ/cm2) were applied to HCE cells. The protein level of IΚBα, Bcl-3 and CTCF were detected by Western analysis. Heterodimer complex of p50/Bcl-3 and their interaction were determined by immunoprecipitation and immunostaining experiments. Promoter activity of CTCF was evaluated by luciferase reporter and ChIP assays.

Results: : We found that expression levels of IΚBα and Bcl-3 presented a diverse fashion in response to EGF and UV stress stimulation. EGF stimulation, but not UV stress, resulted in phosphorylation and degradation of IΚBα, as it typically occurs in the canonical NF-ΚB pathway. In contrast, Bcl-3 in the IΚB family was enhanced by UV exposure to interact with p50. UV stress-induced formation of p50/Bcl-3 complex apparently was the major signaling component in the NF-ΚB pathway in these cells. Bcl-3 bound to the same ΚB site as p50 and p65 were in the CTCF gene promoter region to inhibit CTCF expression. Knockdown of Bcl-3 led to abolish the effect of UV stimulation on suppression of CTCF transcription.

Conclusions: : UV stress-induced Bcl3 activation to form p50/Bcl-3 complex reveals in contrast to EGF that the non-canonical NF-ΚB pathway plays a significant role in stress-induced CTCF regulation in HCE cells.

Keywords: cornea: epithelium • gene/expression • apoptosis/cell death 
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