4.2 Article

A second estrogen receptor from Japanese lamprey (Lethenteron japonicum) does not have activities for estrogen binding and transcription

期刊

GENERAL AND COMPARATIVE ENDOCRINOLOGY
卷 236, 期 -, 页码 105-114

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygcen.2016.07.014

关键词

Lamprey; Estrogen receptor; Evolution

资金

  1. National Institute for Basic Biology Cooperative Research Program [10-335, 11-322]
  2. Ministry of Education, Culture, Sports, Science, and Technology of Japan [23570067, 26440159, 19370027]
  3. Suhara Memorial Foundation
  4. National Science Foundation Graduate Research Fellowship
  5. NSF [IOB-0546906]
  6. NIH [R01-GM081592]
  7. Grants-in-Aid for Scientific Research [26440159, 23570067, 19370027] Funding Source: KAKEN

向作者/读者索取更多资源

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, Esrla and Esrlb 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 (ER alpha) and Esr2 (ER beta) within the jawed vertebrates. Reporter gene assays show that lamprey Esrla 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 Esrla. Unexpectedly, lamprey Esrlb does not bind estradiol and is not stimulated by other estrogens, androgens or corticosteroids. A 3D model of lamprey Esrlb 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 Esrlb. (C) 2016 Elsevier Inc. All rights reserved.

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