Modulation of nuclear receptor function by cellular redox poise.

Area of Science:

• Molecular Biology
• Cellular Signaling
• Biochemistry

Background:

• Nuclear receptors (NRs) are crucial ligand-responsive transcription factors governing diverse cellular processes.
• NRs play roles in metabolism, circadian rhythms, and other vital functions.
• A common feature among NRs is the presence of redox-active thiol groups.

Purpose of the Study:

• To review nuclear receptors (NRs) that possess redox-active thiol groups.
• To elucidate the mechanisms by which thiol-disulfide interconversion regulates NR activity.
• To highlight specific NR examples demonstrating redox regulation.

Main Methods:

• Literature review of nuclear receptors and redox regulation.
• Description of NR structure, function, and ligand/co-factor interactions.
• Detailed examination of redox-sensitive NRs, including glucocorticoid, estrogen, and Rev-erb receptors.

Main Results:

• NR activity is modulated by ligand binding, corepressors, and coactivators.
• Redox regulation, particularly thiol-disulfide exchange, impacts NR function.
• Specific NRs like glucocorticoid, estrogen, and Rev-erb exhibit archetypal redox regulatory mechanisms.

Conclusions:

• Redox-active thiols are integral to the functional regulation of many nuclear receptors.
• Understanding redox modulation of NRs provides insights into cellular signaling pathways.
• This review consolidates knowledge on redox-sensitive NRs, emphasizing key examples.