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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)
Publication Information
Molecules and Cells / v.20, no.2, 2005 , pp. 241-246 More about this Journal
Abstract
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.
Keywords
HDAC1; NF-${\kappa}B$; p65; PDK-1; PI3-Kinase;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 10  (Related Records In Web of Science)
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