Modulation of nuclear receptor function by cellular redox poise.
Nuclear receptors (NRs) are ligand-responsive transcription factors involved in diverse cellular processes ranging from metabolism to circadian rhythms. This review focuses on NRs that contain redox-active thiol groups, a common feature within the superfamily. We will begin by describing NRs, how they regulate various cellular processes and how binding ligands, corepressors and/or coactivators modulate their activity. We will then describe the general area of redox regulation, especially as it pertains to thiol-disulfide interconversion and the cellular systems that respond to and govern this redox equilibrium. Lastly, we will discuss specific examples of NRs whose activities are regulated by redox-active thiols. Glucocorticoid, estrogen, and the heme-responsive receptor, Rev-erb, will be described in the most detail as they exhibit archetypal redox regulatory mechanisms.
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Eric L
EL
Carter
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: sragsdal@umich.edu.
Stephen W
SW
Ragsdale
D004220:Disulfides / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009688:Nuclear Reactors; D010084:Oxidation-Reduction; D011485:Protein Binding; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004220:Disulfides; D008024:Ligands; D013438:Sulfhydryl Compounds; D014157:Transcription Factors; D006418:Heme
Hormone; Nuclear receptor; Oxidative stress; Redox; Thiol–disulfide; Transcription