Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Role of PI3-Kinase/Akt Pathway in the Activation of Etoposide-Induced $NF-{\kappa}B$ Transcription Factor

  • Choi Yong-Seok (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University) ;
  • Park Heon-Yong (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University) ;
  • Jeong Sun-Joo (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University)
  • Published : 2006.03.01
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Abstract

$NF-{\kappa}B$ is a transcription factor involved in the innate immunity against bacterial infection and inflammation. It is also known to render cells resistant to the apoptosis caused by some anticancer drugs. Such a chemoresistance of cancer cells may be related to the activation of $NF-{\kappa}B$ transcription factor; however, the mechanism of activation is not well understood. Here, we demonstrate that a chemotherapeutic agent, etoposide, independently stimulates the $I{\kappa}B{\alpha}$ degradation pathway and PI3-kinase/Akt signaling pathway: The classical $I{\kappa}B{\alpha}$ degradation pathway leads to the nuclear translocation and DNA binding of p65 subunit through $IKK{\beta}$ kinase, whereas the PI3-kinase/Akt pathway plays a distinct role in activating this transcription factor. The PI3-kinase/Akt pathway acts on the p50 subunit of the $NF-{\kappa}B$ transcription factor and enhances the DNA binding affinity of the p50 protein. It may also explain the role of the PI3-kinase/Akt pathway in the anti-apoptotic function of $NF-{\kappa}B$ during chemoresistance of cancer cells.

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References

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