|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4whg' size='340' side='right'caption='[[4whg]], [[Resolution|resolution]] 2.18Å' scene=''> | | <StructureSection load='4whg' size='340' side='right'caption='[[4whg]], [[Resolution|resolution]] 2.18Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4whg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WHG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4whg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WHG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3NB:1-(3,4,5-TRIHYDROXYPHENYL)OCTAN-1-ONE'>3NB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3NB:1-(3,4,5-TRIHYDROXYPHENYL)OCTAN-1-ONE'>3NB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4whf|4whf]], [[4re8|4re8]], [[4ree|4ree]], [[4ref|4ref]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4whg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4whg OCA], [https://pdbe.org/4whg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4whg RCSB], [https://www.ebi.ac.uk/pdbsum/4whg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4whg ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR4A1, GFRP1, HMR, NAK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4whg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4whg OCA], [http://pdbe.org/4whg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4whg RCSB], [http://www.ebi.ac.uk/pdbsum/4whg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4whg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NR4A1_HUMAN NR4A1_HUMAN]] Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.<ref>PMID:15466594</ref> | + | [https://www.uniprot.org/uniprot/NR4A1_HUMAN NR4A1_HUMAN] Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.<ref>PMID:15466594</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cai, Q X]] | + | [[Category: Cai QX]] |
| - | [[Category: Hou, P P]] | + | [[Category: Hou PP]] |
| - | [[Category: Li, A Z]] | + | [[Category: Li AZ]] |
| - | [[Category: Li, F W]] | + | [[Category: Li FW]] |
| - | [[Category: Lin, T W]] | + | [[Category: Lin TW]] |
| - | [[Category: Tian, X Y]] | + | [[Category: Tian XY]] |
| - | [[Category: Wang, W J]] | + | [[Category: Wang WJ]] |
| - | [[Category: Wang, Y]] | + | [[Category: Wang Y]] |
| - | [[Category: Wu, Q]] | + | [[Category: Wu Q]] |
| - | [[Category: Lbd]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
NR4A1_HUMAN Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.[1]
Publication Abstract from PubMed
Apoptotic resistance is becoming a significant obstacle for cancer therapy as the majority of treatment takes the route of apoptotic induction. It is of great importance to develop an alternative strategy to induce cancer cell death. We previously reported that autophagic cell death mediated by nuclear receptor TR3 and driven by a chemical agonist, 1-(3,4,5-trihydroxyphenyl)nonan-1-one (THPN), is highly effective in the therapy of melanoma but not any other cancer types. Here, we discovered that the insensitivity of cancer cells to THPN originated from a high cellular Akt2 activity. Akt2 phosphorylation interferes with TR3 export to cytoplasm and targeting to mitochondria, which lead to the autophagic induction. Therefore, the TR3-mediated autophagy could be effectively induced in the otherwise insensitive cells by downregulating Akt2 activity. Highly effective antineoplastic compounds are developed through optimizing the structure of THPN. This study implicates a general strategy for cancer therapy by the induction of autophagic cell death.
Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity.,Wang WJ, Wang Y, Hou PP, Li FW, Zhou B, Chen HZ, Bian XL, Cai QX, Xing YZ, He JP, Zhang H, Huang PQ, Lin T, Wu Q Chem Biol. 2015 Aug 20;22(8):1040-51. doi: 10.1016/j.chembiol.2015.06.023. Epub, 2015 Jul 30. PMID:26235054[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harant H, Lindley IJ. Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic Acids Res. 2004 Oct 5;32(17):5280-90. Print 2004. PMID:15466594 doi:10.1093/nar/gkh856
- ↑ Wang WJ, Wang Y, Hou PP, Li FW, Zhou B, Chen HZ, Bian XL, Cai QX, Xing YZ, He JP, Zhang H, Huang PQ, Lin T, Wu Q. Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity. Chem Biol. 2015 Aug 20;22(8):1040-51. doi: 10.1016/j.chembiol.2015.06.023. Epub, 2015 Jul 30. PMID:26235054 doi:http://dx.doi.org/10.1016/j.chembiol.2015.06.023
|
