Nuclear receptors versus inflammation: mechanisms of transrepression.
Inflammation is a beneficial host response to external challenge or cellular injury that leads to the activation of a complex array of inflammatory mediators, finalizing the restoration of tissue structure and function. Although a beneficial response, prolonged inflammation can be detrimental to the host, contributing to the pathogenesis of many disease states. Considerable attention has been focused on the ability of several members of the nuclear receptor superfamily to inhibit transcriptional activation by signal-dependent transcription factors that include nuclear factor kappaB and activator protein 1, thereby, attenuating inflammatory responses to both acute and chronic challenge. An important general mechanism responsible for this activity is referred to as transrepression, in which nuclear receptors interfere with signal-dependent activation of inflammatory response genes through protein-protein interactions with coregulatory proteins and promoter-bound transcription factors, rather than direct, sequence-specific interactions with DNA.
Pascual
Gabriel
G
Department of Cellular and Molecular Medicine, Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.
Glass
Christopher K
CK
D000818:Animals; D015536:Down-Regulation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000517:prevention & control*; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000502:physiology
C539127:NCOR1 protein, human; D016328:NF-kappa B; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D018808:Transcription Factor AP-1