Biology:Liver X receptor alpha

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene (nuclear receptor subfamily 1, group H, member 3).[1][2]

Expression

miRNA hsa-miR-613 autoregulates the human LXRα gene by targeting the endogenous LXRα through its specific miRNA response element (613MRE) within the LXRα 3′-untranslated region. LXRα autoregulates its own suppression via induction of SREBP1c which upregulates miRNA has-miR-613.[3]

Function

The liver X receptors, LXRα (this protein) and LXRβ, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. Additionally, they play an important role in the local activation of thyroid hormones via deiodinases.[4] The inducible LXRα is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRβ is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs) and regulate expression of target genes containing LXR response elements.[5][6] Restoration of LXR-alpha expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin.[7]

Interactions

Liver X receptor alpha has been shown to interact with EDF1[8] and Small heterodimer partner.[9] LXRα activates the transcription factor SREBP-1c, resulting in lipogenesis.[10]

Link to multiple sclerosis

In 2016, a study found 70% of individuals in two families with a rare form of rapidly progressing multiple sclerosis had a mutation in NR1H3.[11] However, an analysis from The International Multiple Sclerosis Genetics Consortium using a 13-fold larger sample size could not find any evidence that the mutation in question (p.Arg415Gln) associated with multiple sclerosis, refuting these findings.[12]

References

  1. ↑ "The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling". The Journal of Biological Chemistry 271 (16): 9189–92. Apr 1996. doi:10.1074/jbc.271.16.9189. PMID 8621574. 
  2. ↑ "LXR, a nuclear receptor that defines a distinct retinoid response pathway". Genes & Development 9 (9): 1033–45. May 1995. doi:10.1101/gad.9.9.1033. PMID 7744246. 
  3. ↑ http://mend.endojournals.org/content/25/4/584.abstract [|permanent dead link|dead link}}]
  4. ↑ "Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway". The Journal of Endocrinology 205 (2): 179–86. 2010. doi:10.1677/JOE-09-0448. PMID 20176747. 
  5. ↑ "Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice". The Journal of Clinical Investigation 119 (6): 1626–37. Jun 2009. doi:10.1172/JCI35288. PMID 19436111. 
  6. ↑ "Entrez Gene: nuclear receptor subfamily 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10062. 
  7. ↑ "Psoriasis: crucial role of LXR-alpha RNomics". Genes and Immunity 11 (1): 37–44. Jan 2010. doi:10.1038/gene.2009.63. PMID 19798078. 
  8. ↑ "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology 16 (6): 1367–77. Jun 2002. doi:10.1210/mend.16.6.0843. PMID 12040021. 
  9. ↑ "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology 16 (9): 2065–76. Sep 2002. doi:10.1210/me.2001-0194. PMID 12198243. 
  10. ↑ "Leptin therapy in insulin-deficient type I diabetes". Proceedings of the National Academy of Sciences of the United States of America 107 (11): 4813–9. 2010. doi:10.1073/pnas.0909422107. PMID 20194735. 
  11. ↑ "Nuclear Receptor NR1H3 in Familial Multiple Sclerosis". Neuron 90 (5): 948–54. 2016. doi:10.1016/j.neuron.2016.04.039. PMID 27253448. 
  12. ↑ "NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk". Neuron 92 (2): 333–335. October 2016. doi:10.1016/j.neuron.2016.09.052. PMID 27764667. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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