Redox control of protein-DNA interactions: from molecular mechanisms to significance in signal transduction, gene expression, and DNA replication.
Protein-DNA interactions play a key role in the regulation of major cellular metabolic pathways, including gene expression, genome replication, and genomic stability. They are mediated through the interactions of regulatory proteins with their specific DNA-binding sites at promoters, enhancers, and replication origins in the genome. Redox signaling regulates these protein-DNA interactions using reactive oxygen species and reactive nitrogen species that interact with cysteine residues at target proteins and their regulators. This review describes the redox-mediated regulation of several master regulators of gene expression that control the induction and suppression of hundreds of genes in the genome, regulating multiple metabolic pathways, which are involved in cell growth, development, differentiation, and survival, as well as in the function of the immune system and cellular response to intracellular and extracellular stimuli. It also discusses the role of redox signaling in protein-DNA interactions that regulate DNA replication. Specificity of redox regulation is discussed, as well as the mechanisms providing several levels of redox-mediated regulation, from direct control of DNA-binding domains through the indirect control, mediated by release of negative regulators, regulation of redox-sensitive protein kinases, intracellular trafficking, and chromatin remodeling.
Shlomai
Joseph
J
Department of Microbiology and Molecular Genetics, The Kuvin Center for the Study of Tropical and Infectious Diseases, Institute for Medical Research Canada-Israel, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. josephs@ekmd.huji.ac.il
D002453:Cell Cycle; D049109:Cell Proliferation; D004261:DNA Replication; D018105:DNA, Kinetoplast / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D010084:Oxidation-Reduction; D011494:Protein Kinases / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018105:DNA, Kinetoplast; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases