Biology:TLX
 Generic protein structure example |
Nuclear receptor TLX (homologue of the Drosophila tailless gene) also known as NR2E1 (Nuclear receptor subfamily 2 group E member 1) is a protein that in humans is encoded by the NR2E1 gene.[1] TLX is a member of the nuclear receptor family of intracellular transcription factors.
Function
TLX regulates the expression of another nuclear receptor, RAR.[2]
TLX also is essential for normal brain-eye coordination and appears to play a role in control of aggressive behavior.[3]
Adult neural stem cells are nuclear receptor TLX-positive and TLX expression in these cells is crucial in maintaining their undifferentiated state.[4] Furthermore, TLX regulates adult neural stem cell proliferation. Removal of TLX from the adult mouse brain resulted in a reduction of stem cell proliferation and spatial learning.[5]
Tlx-positive cells of the subventricular zone of adult mouse brain are self-renewing stem cells. Mutation of the Tlx gene in adult mouse brain leads to complete loss of neurogenesis in the subventricular zone. Tlx is also required for transition from radial glial cells to astrocyte-like neural stem cells.[6]
Ligands
TLX belongs to a small family of NRs that lack two helices in the ligand-binding domain, forming an enlarged binding pocket. Three compounds, termed ccrp1–3 (famprofazone, 1-(1,5-dimethylpyrazole-3-carbonyl)-4-(diphenylmethyl)piperazine, dydrogesterone), have been discovered in high-throughput screening that enhance TLX's ability of transcription repression with high potency.[7]
References
- ↑ "The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21". Genomics 50 (1): 34–43. May 1998. doi:10.1006/geno.1998.5270. PMID 9628820.
- ↑ "Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX". Molecular and Cellular Biology 20 (23): 8731–9. December 2000. doi:10.1128/MCB.20.23.8731-8739.2000. PMID 11073974.
- ↑ "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1". The Journal of Neuroscience 25 (27): 6263–70. July 2005. doi:10.1523/JNEUROSCI.4757-04.2005. PMID 16000615. PMC 6725287. http://www.jneurosci.org/content/jneuro/25/27/6263.full.pdf.
- ↑ "Expression and function of orphan nuclear receptor TLX in adult neural stem cells". Nature 427 (6969): 78–83. January 2004. doi:10.1038/nature02211. PMID 14702088. Bibcode: 2004Natur.427...78S.
- ↑ "A role for adult TLX-positive neural stem cells in learning and behaviour". Nature 451 (7181): 1004–7. February 2008. doi:10.1038/nature06562. PMID 18235445. Bibcode: 2008Natur.451.1004Z.
- ↑ "The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone". Genes & Development 22 (18): 2473–8. September 2008. doi:10.1101/gad.479308. PMID 18794344.
- ↑ "The human orphan nuclear receptor tailless (TLX, NR2E1) is druggable". PLOS ONE 9 (6): e99440. 2014. doi:10.1371/journal.pone.0099440. PMID 24936658. Bibcode: 2014PLoSO...999440B.
Further reading
- "Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx". Nature 370 (6488): 375–9. August 1994. doi:10.1038/370375a0. PMID 8047143. Bibcode: 1994Natur.370..375Y.
- "Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX". Molecular and Cellular Biology 20 (23): 8731–9. December 2000. doi:10.1128/MCB.20.23.8731-8739.2000. PMID 11073974.
- "Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci". Genomics 80 (1): 45–53. July 2002. doi:10.1006/geno.2002.6795. PMID 12079282.
- "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1". The Journal of Neuroscience 25 (27): 6263–70. July 2005. doi:10.1523/JNEUROSCI.4757-04.2005. PMID 16000615. PMC 6725287. http://www.jneurosci.org/content/jneuro/25/27/6263.full.pdf.
- "Mutation and evolutionary analyses identify NR2E1-candidate-regulatory mutations in humans with severe cortical malformations". Genes, Brain, and Behavior 6 (6): 503–16. August 2007. doi:10.1111/j.1601-183X.2006.00277.x. PMID 17054721.
- "Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes". BMC Medical Genetics 8: 48. July 2007. doi:10.1186/1471-2350-8-48. PMID 17655765.
- "Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation". Proceedings of the National Academy of Sciences of the United States of America 104 (39): 15282–7. September 2007. doi:10.1073/pnas.0704089104. PMID 17873065. Bibcode: 2007PNAS..10415282S.
External links
- NR2E1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
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