The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRβ in the hepatic acute phase response
Abstract
The orphan receptor LRH-1 and the oxysterol receptors LXRα and LXRβ are established transcriptional regulators of lipid metabolism that appear to control inflammatory processes. Here, we investigate the anti-inflammatory actions of these nuclear receptors in the hepatic acute phase response (APR). We report that selective synthetic agonists induce SUMOylation-dependent recruitment of either LRH-1 or LXR to hepatic APR promoters and prevent the clearance of the N-CoR corepressor complex upon cytokine stimulation. Investigations of the APR in vivo, using LXR knockout mice, indicate that the anti-inflammatory actions of LXR agonists are triggered selectively by the LXRβ subtype. We further find that hepatic APR responses in small ubiquitin-like modifier-1 (SUMO-1) knockout mice are increased, which is due in part to diminished LRH-1 action at APR promoters. Finally, we provide evidence that the metabolically important coregulator GPS2 functions as a hitherto unrecognized transrepression mediator of interactions between SUMOylated nuclear receptors and the N-CoR corepressor complex. Our study extends the knowledge of anti-inflammatory mechanisms and pathways directed by metabolic nuclear receptor–corepressor networks to the control of the hepatic APR, and implies alternative pharmacological strategies for the treatment of human metabolic diseases associated with inflammation.
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LXRs become SUMOylated in the presence of ligands, repressing inflammatory target genes.
“LXRs as the oxysterol-sensitive nuclear receptors become SUMOylated in the presence of endogenous and/or synthetic ligands, thereby repressing the transcription of inflammatory target genes in multiple cell types (33, 34, 35).”
From SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1 (2021) · cites this paper as [34]
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Cites
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“Interestingly, at least in interferon-stimulated brain astrocytes, both LXR subypes can also be differentially modified (Lee et al. 2009).”
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Research works printed but not linked: 26
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Ito, A., Hong, C., Rong, X., Zhu, X., Tarling, E. J., Hedde, P. N., Gratton, E., Parks, J., & Tontonoz, P. (2015) · eLife · doi:10.7554/elife.08009 · Cited by 281
“Key features of this model include the requirement for receptor SUMOylation, the involvement of an LXR monomer, and the mechanistic separation of the transcriptional activation and repression functions of LXRs (Ghisletti et al., 2007; Lee et al., 2009; Venteclef et al., 2010).”
BackgroundCommon dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases
Narayanan, M., Huynh, J. L., Wang, K., Yang, X., Yoo, S., McElwee, J., Zhang, B., Zhang, C., Lamb, J. R., Xie, T., et al. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145304 · Cited by 208
A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity
Kim, D., Xiao, Z., Kwon, S., Sun, X., Ryerson, D., Tkac, D., Ma, P., Wu, S., Chiang, C., Zhou, E., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201489527 · Cited by 126
Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA
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Self-citationMetabolic nuclear receptor signaling and the inflammatory acute phase response
Venteclef, N., Jakobsson, T., Steffensen, K. R., & Treuter, E. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.04.004 · Cited by 99
Self-citationNuclear receptors linking metabolism, inflammation, and fibrosis in nonalcoholic fatty liver disease
Puengel, T., Liu, H., Guillot, A., Heymann, F., Tacke, F., & Peiseler, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052668 · Cited by 95
SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1
Wang, J.-Q., Lin, Z.-C., Li, L.-L., Zhang, S.-F., Li, W.-H., Liu, W., Song, B.-L., & Luo, J. (2021) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015420 · Cited by 24
Metadata
- Authors
- Venteclef, N., Jakobsson, T., Ehrlund, A., Damdimopoulos, A., Mikkonen, L., Ellis, E., Nilsson, L.-M., Parini, P., Jänne, O. A., Gustafsson, J.-Å., Steffensen, K. R., & Treuter, E.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-02-15
- Volume
- 24
- Issue
- 4
- Pages
- 381-395
- ISSN
- 0890-9369
- 1549-5477
- Cited by
- 178
- References
- 5
- Language
- en
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