A second estrogen receptor from Japanese lamprey (Lethenteron japonicum) does not have activities for estrogen binding and transcription
| Autor: | Charlie Chandsawangbhuwana, Joseph W. Thornton, Rui Sato, Yoshio Takei, Koari Oka, Taisen Iguchi, Michael E. Baker, Paul A. Cziko, Yoshinao Katsu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lethenteron medicine.medical_specialty medicine.drug_class Estrogen receptor Evolution Molecular 03 medical and health sciences Endocrinology Japan Internal medicine biology.animal medicine Animals Humans Estrogen binding Transcription factor Phylogeny biology Lamprey Lampreys Vertebrate biology.organism_classification Cell biology 030104 developmental biology Receptors Estrogen Estrogen Animal Science and Zoology human activities Estrogen receptor alpha |
| Zdroj: | General and Comparative Endocrinology. 236:105-114 |
| ISSN: | 0016-6480 |
| Popis: | Estrogens regulate many physiological responses in vertebrates by binding to the estrogen receptor (ER), a ligand-activated transcription factor. To understand the evolution of vertebrate ERs and to investigate how estrogen acts in a jawless vertebrate, we used degenerate primer sets and PCR to isolate DNA fragments encoding two distinct ER subtypes, Esr1a and Esr1b from the Japanese lamprey, Lethenteron japonicum. Phylogenetic analysis indicates that these two ERs are the result of lineage-specific gene duplication within the jawless fishes, different from the previous duplication event of Esr1 (ERα) and Esr2 (ERβ) within the jawed vertebrates. Reporter gene assays show that lamprey Esr1a displays both constitutive and estrogen-dependent activation of gene transcription. Domain swapping experiments indicate that constitutive activity resides in the A/B domain of lamprey Esr1a. Unexpectedly, lamprey Esr1b does not bind estradiol and is not stimulated by other estrogens, androgens or corticosteroids. A 3D model of lamprey Esr1b suggests that although estradiol fits into the steroid binding site, some stabilizing contacts between the ligand and side chains that are found in human Esr1 and Esr2 are missing in lamprey Esr1b. |
| Databáze: | OpenAIRE |
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