4ree

Crystal Structure of TR3 LBD in complex with Molecule 6

spinqualitylabelsall models 4ree, resolution 2.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ree is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.37Å Ligands: 3MZ, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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