PI3K, RSK, and mTOR signal networks for the GST gene regulation.
The induction of glutathione S-transferases (GST) represents not only cell detoxification and survival but also cancer prevention. In response to various extracellular stimuli, expression of the gene has been shown to be regulated coordinately by activating the transcription factors in a transcriptional or posttranscriptional manner. Cytoprotective agents induce GST and concomitantly activate the PI3K-Akt/ERK-RSK1-mTOR pathways that activate the transcription factors favoring cell viability. The mechanistic basis and cell signaling for the induction of GST induction by prooxidants and toxicants may be different from that by cytoprotective agents. This paper summarizes the molecular mechanisms of the transcriptional induction of the GST gene orchestrated by a series of transcription factors that recruit coactivators or corepressors.
Kim
Sang Geon
SG
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea. sgk@snu.ac.kr
Lee
Seung Jin
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D000975:Antioxidants; D005982:Glutathione Transferase; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human