Molecules and Cells

  • 제20권2호
  • /
  • Pages.241-246
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  • 2005
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

PI3-Kinase and PDK-1 Regulate HDAC1-mediated Transcriptional Repression of Transcription Factor NF-κB

  • Choi, Yong Seok (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University) ;
  • Jeong, Sunjoo (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University)
  • 투고 : 2005.05.23
  • 심사 : 2005.06.07
  • 발행 : 2005.10.31
⟨ 이전 논문 다음 논문 ⟩

초록

PDK-1 activates PI3-kinase/Akt signaling and regulates fundamental cellular functions, such as growth and survival. NF-${\kappa}B$ is involved in the induction of a variety of cellular genes affecting immunity, inflammation and the resistance to apoptosis induced by some anti-cancer drugs. Even though the crucial involvement of the PI3-kinase/Akt pathway in the anti-apoptotic activation of NF-${\kappa}B$ is well known, the exact role of PDK-1 as well as PI3-kinase/Akt in NF-vactivation is not understood. Here we demonstrate that PDK-1 plays a pivotal role in transcriptional activation of NF-${\kappa}B$ by dissociating the transcriptional co-repressor HDAC1 from the p65 subunit of NF-${\kappa}B$. The association of CBP with p65 was not directly modulated by PDK-1 or by PI3-kinase. Etoposide activated NF-${\kappa}B$ through PI3-kinase/Akt, and the transcription activation domain (TAD) of p65 was further activated by wild-type PDK-1. Overexpression of a dominant negative PDK-1 mutant decreased etoposide-induced NF-${\kappa}B$ transcription and further down-regulated the ectopic HDAC1-mediated decrease in NF-${\kappa}B$ transcriptional activity. Thus activation of PDK-1 relieves the HDAC1-mediated repression of NF-${\kappa}B$ that may be related to basal as well as activated transcription by NF-${\kappa}B$. This effect may also explain the role of the PI3-kinase/PDK-1 pathway in the anti-apoptotic function of NF-${\kappa}B$ associated with the chemoresistance of cancer cells.

키워드

과제정보

연구 과제 주관 기관 : Dankook University

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