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dc.contributor.authorKhalturin, Konstantin  Concept link
dc.contributor.authorBillas, Isabelle M. L.  Concept link
dc.contributor.authorChebaro, Yassmine  Concept link
dc.contributor.authorReitzel, Adam M.  Concept link
dc.contributor.authorTarrant, Ann M.  Concept link
dc.contributor.authorLaudet, Vincent  Concept link
dc.contributor.authorMarkov, Gabriel V.  Concept link
dc.date.accessioned2018-09-21T15:10:48Z
dc.date.available2018-09-21T15:10:48Z
dc.date.issued2018-06
dc.identifier.urihttps://hdl.handle.net/1912/10583
dc.descriptionAuthor Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Journal of Steroid Biochemistry and Molecular Biology 184 (2018): 11-19, doi:10.1016/j.jsbmb.2018.06.014.en_US
dc.description.abstractSteroid hormone receptors are important regulators of development and physiology in bilaterian animals, but the role of steroid signaling in cnidarians has been contentious. Cnidarians produce steroids, including A-ring aromatic steroids with a side-chain, but these are probably made through pathways different than the one used by vertebrates to make their A-ring aromatic steroids. Here we present comparative genomic analyses indicating the presence of a previously undescribed nuclear receptor family within medusozoan cnidarians, that we propose to call NR3E. This family predates the diversification of ERR/ER/SR in bilaterians, indicating that the first NR3 evolved in the common ancestor of the placozoan and cnidarian-bilaterian with lineage-specific loss in the anthozoans, even though multiple species in this lineage have been shown to produce aromatic steroids, whose function remain unclear. We discovered serendipitously that a cytoplasmic factor within epidermal cells of transgenic Hydra vulgaris can trigger the nuclear translocation of heterologously expressed human ERα. This led us to hypothesize that aromatic steroids may also be present in the medusozoan cnidarian lineage, which includes Hydra, and may explain the translocation of human ERα. Docking experiments with paraestrol A, a cnidarian A-ring aromatic steroid, into the ligand-binding pocket of Hydra NR3E indicates that, if an aromatic steroid is indeed the true ligand, which remains to be demonstrated, it would bind to the pocket through a partially distinct mechanism from the manner in which estradiol binds to vertebrate ER.en_US
dc.description.sponsorshipKK is supported by grant from Japan Society for the Promotion of Science (JSPS 17K07420). I.M.L.B and Y.C. acknowledge the support and the use of resources of the French Infrastructure for Integrated Structural Biology FRISBI ANR-10-INBS-05 and of Instruct-ERIC. AMR was supported by NIH Award R15GM114740. AMT was supported by an Internal Research and Development Award from the Woods Hole Oceanographic Institution.en_US
dc.language.isoen_USen_US
dc.relation.urihttps://doi.org/10.1016/j.jsbmb.2018.06.014
dc.subjectA-ring aromatic steroiden_US
dc.subjectAromatizationen_US
dc.subjectSteroid receptoren_US
dc.subjectCnidarianen_US
dc.titleNR3E receptors in cnidarians : a new family of steroid receptor relatives extends the possible mechanisms for ligand bindingen_US
dc.typePreprinten_US


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