Table 1. Human lipid sensors.
| Lipid-Sensors | ||||||||
|---|---|---|---|---|---|---|---|---|
| Gene | Chr (No) | Exons (No) | Protein-variant | Prot (aa) | DBD (aa No) | LBD (aa No) | Ligands | Predicted action in breast-cancer |
|
NR1C1 (PPARα) Peroxysome-Proliferator-Activated-Receptor-α |
22 | 8 | NP_001001928 | 468 | 101-184 | 201-467 | 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PUBCHEM:65167)(end. agonist) Chakravarthy MV et al, Cell(2009)138:476-88 CP775146 (PUBCHEM:10410059)(synth. agonist) Kane CD et al, Mol Pharmacol (2009)75:296-306 GW6471 (PUBCHEM:446738)(synth. antagonist) Muller MQ et al, J Med Chem (2009)52:2875-9 |
Mixed results |
|
NR1C2 (PPARβ/δ) Peroxysome-Proliferator-Activated-Receptor-β/δ |
6 | 8 7 6 8 |
NP_006229 NP_001165290 NP_001165291 NP_803184 |
441 402 343 361 |
73-156 34-117 41-58 73-156 |
173-440 134-401 75-342 173-359 |
PGI2 (PUBCHEM:23702145)(end. agonist) Gupta RA et al, Proc Natl Acad Sci U S A (2000)97:13275-80 15-HETE (PUBCHEM:9966861)(end. agonist) Naruhn S et al, Mol Pharmacol (2010) 77:171-84 Fatty-acids (end. agonists) Barish GD et al, J Clin Invest (2006)116:590-7 GW0742 (PUBCHEM:9934458)(synth. agonist) Sznaidman L et al, Bioorg Med Chem Lett (2003)13:1517-21 GSK3787 (PUBCHEM:2800647)(synth. antagonist) Palkar PS et al, Mol Pharmacol (2010)78:419-30 |
Oncogenic action Her2 tumors |
|
NR1C3 (PPARγ) Peroxysome-Proliferator-Activated-Receptor-γ |
3 | 8 7 |
NP_619725 NP_056953 |
477 505 |
110-193 138-221 |
209-476 237-504 |
15-deoxy-Δ12,14-PGJ2 (PUBCHEM:5311211)(end. agonist) Kotta-Loizou IC et al, Anticancer Agents Med Chem (2012)12:1025-44 Unsatur. fatty-acids (end. agonists) Troglitazone (PUBCHEM:5591)(synth. agonists) Kodera Y et al, J Biol Chem (2000)275:33201-4 BADGE (PUBCHEM:3479589)(synth. antagonist) Bishop-Bailey D et al, Br J Pharmacol (2000) 131:651-4 |
Onco-suppressive action |
|
NR1H2 (LXRβ) Liver-X-Receptor-β |
19 | 10 9 |
NP_009052 NP_001243576 |
461 364 |
67-163 - |
224-459 127-362 |
27-hydroxycholesterol (PUBCHEM:123976)(end. agonist) Song C et al, Steroids (2000)65:423-7 Oxysterols (end. agonists) Zhao C and Dahlman-Wright K, J Endocrinol (2010)204:233-40 GW3965 (PUBCHEM:447905)(synth. agonist) Collins JL et al, J Med Chem(2002)45:1963-6 GSK2033 (PUBCHEM:46203250)(synth. antagonist) Zuercher WJ et al, J Med Chem (2010)53:3412-6 |
Onco-suppressive action |
|
NR1H3 (LXRα) Liver-X-Receptor-α |
11 | 10 10 9 9 |
NP_001238863 NP_005684 NP_001123574 NP_001123573 |
453 447 402 387 |
84-184 78-178 33-133 78-187 |
216-451 210-445 165-400 210-385 |
27-hydroxycholesterol (PUBCHEM:123976)(end. agonist) Song C et al, Steroids (2000)65:423-7 Oxysterols (end. agonists) Zhao C and Dahlman-Wright K, J Endocrinol (2010)204:233-40 GW3965 (PUBCHEM:447905)(synth. agonists) Collins JL et al, J Med Chem(2002)45:1963-6 GSK2033 (PUBCHEM:46203250)(synth. antagonist) Zuercher WJ et al, J Med Chem (2010)53:3412-6 |
Onco-suppressive action |
|
NR1H4 (FXR) Farnesoid-X-Receptor |
12 | 11 11 10 9 9 |
NP_005114 NP_001193908 NP_001193907 NP_001193921 NP_001193922 |
472 476 425 482 486 |
124-207 124-211 127-149 134-217 134-221 |
247-467 251-471 200-420 252-470 256-474 |
Deoxycholate (PUBCHEM:23668196)(end. agonist) Silva J et al, J Lipid Res (2006) 47:724-33 Chenodeoxycholic-acid (PUBCHEM:10133)(end. agonist) Makishima M et al, Science (1999) 284:1362-5 GW4064 (PUBCHEM:9893571)(synth. agonist) Maloney PR et al, J Med Chem (2000) 43:2971-4 guggulsterone (PUBCHEM:6439929)(synth. antagonist) Owsley E and Chiang JY, Biochem Biophys Res Commun (2003) 304:191-5 |
Mixed results |
|
NR1I2 (PXR) Pregnane-X-Receptor |
3 | 9 9 9 |
NP_003880 NP_148934 NP_071285 |
434 397 473 |
40-127 40-127 79-166 |
143-428 143-391 182-467 |
Rifampicin (PUBCHEM:6913622)(synth. agonist) Moore LB et al, J Biol Chem (2000) 275:15122-7 SR12813 (PUBCHEM:446313) (synth. agonist) Lemaire G et al, Mol Pharmacol (2007) 72:572-81 Meclizine (PUBCHEM:4034)(synth. antagonist) Lau AJ et al, J Pharmacol Exp Ther(2011) 336:816-26 |
Oncogenic action |
The table contains basic information on the characteristics of the Lipid-Sensors group of nuclear receptors (NRs). The first column lists the human NRs considered in the review article. The official symbol of each NR is indicated in italics, while the original alias of each protein product is indicated in parenthesis. The full name of each NR is indicated underneath in italics. The second column from the left lists the human chromosome (Chr) each NR maps to. The number of exons encoding the transcripts giving rise to the corresponding NR protein-variant is indicated in the third column. The fourth column lists the accession number of each NR protein-variant. The amino acid (aa) length of each NR protein variant, the position of the DNA-binding domain (DBD) and the ligand-binding domain (LBD) are indicated in columns five, six and seven, respectively. Column eight contains a list of representative endogenous (end.) and synthetic (synth.) agonists, antagonists and reverse agonists for each NR along with an appropriate reference. The chemical structures of the listed molecules can be found in the PUBCHEM database with the use of the PUBCHEM-CID accession numbers provided. The PUBCHEM chemical structure is not available in the case of the NR2E1 agonists Ccrp-1, -2 and -3. When possible, the predicted onco-suppressive (bold) or oncogenic (black-boxed) action of the corresponding NR is indicated in the last column on the right. Synthetic agonists and antagonists of potential therapeutic interested targeting onco-suppressive and oncogenic NRs, respectively, are marked in bold and boxed in black. Finally, in the few cases where supportive data are available, the type of breast-cancer which is predicted to represent a preferential target of the NR is listed in the last column.