An example of glucocorticoid transrepression
is the effect on bone metabolism.
Moreover, PPARs have been proposed to physically cross-inhibit inflammatory transcription factors, such as NF-[kappa]B, AP-1, signal transducers and activators of transcription (STATs), and NFAT, in a process termed "transrepression
GR[beta] acts as a dominant-negative inhibitor of GR[alpha]-mediated transactivation and transrepression
in certain cell types.
This mechanism of inhibitory action by the AhRR is thought to be independent of competition for ARNT and may involve transrepression
mechanism as hypothesized previously (Evans et al.
Glass, "An ADIOL-ER/5-CtBP transrepression
pathway negatively regulates microglia-mediated inflammation," Cell, vol.
In addition to its effects on lipid metabolism, PPAR[gamma] dampens inflammation via transrepression
of proinflammatory molecules .
Therefore, the transrepression
activity of PPAR[alpha] on lipid biosynthesis and anaplerosis is just as relevant as its transactivation activity on FAO genes.
Alternatively, p53 can mediate transrepression
by preventing the binding of other transcriptional activators to their target sites .
ER[alpha]-AHRARNT protein-protein interactions mediate estradiol-dependent transrepression
of dioxininducible gene transcription.
Interestingly PPAR-[gamma] was the first reported to undergo agonist-dependent simulation, which promotes binding to nuclear receptor co-repressor-1 protein (NCoR) and stabilizes association with promoter-bound NF-[kappa]B, thereby leading to the transrepression
of inflammatory genes in macrophages [86-88].
The negative regulation of inflammatory responses is mediated by the inhibition of transcription factors, for example, NF-[kappa]B, activator protein-1 (AP-1), members of the signal transducer and activator of transcription (STAT) protein family, and nuclear factor of activated T cells (NFAT), often via a mechanism termed transrepression
of proinflammatory cytokines by PPAR-[gamma] via inhibition of NF-[kappa]B is a mechanism that has been closely linked to the PPAR-[gamma]-mediated improvement of organ injury, including the heart, by eliminating systemic inflammation in sepsis [14, 15].