title: Nucleolar Sik-similar protein (Sik-SP) is required for the maintenance of uterine estrogen signaling mechanism via ERα.
abstract: Sik-similar protein (Sik-SP), a small nucleolar ribonucleoprotein, has been shown to be primarily involved in ribosome biogenesis. However, its role in the hormone-directed nuclear receptor signaling is largely unknown. Here, we provide novel evidence that Sik-SP is required for appropriate regulation of estrogen receptor (ER)α-mediated estradiol-17β (E2)-dependent uterine physiologic responses in mice. Studies by Western blotting using the newly developed antibodies for Sik-SP showed that this protein is up-regulated in both the ovariectomized wild-type and ERα null uteri by E2. Immunohistochemical analyses in uterine sections showed that this protein is induced in the epithelial and stromal cells. Coimmunoprecipitation studies revealed that E2 directs molecular interaction between Sik-SP and ERα. Furthermore, gel-mobility shift and chromatin immunoprecipitation analyses provided evidence that Sik-SP is recruited with ERα to estrogen-responsive uterine gene promoters. Overexpression of Sik-SP in vitro demonstrated a role for Sik-SP in cellular growth and viability. In a primary uterine epithelial-stromal coculture system, E2 exhibited early induction of Sik-SP in both the epithelial and stromal cells. Interestingly, suppression of Sik-SP in this coculture model, for the stromal but not epithelial cells, caused perturbation of E2-dependent proliferation in the epithelial cell layer. Similarly, in vivo uterine suppression of Sik-SP also caused inhibition of epithelial cell proliferation and aberrant prolongation of water imbibition in the late phase by E2. Finally, studies showed that Sik-SP is physiologically important during the onset of implantation by E2. In conclusion, Sik-SP, an early E2-responsive nucleolar protein, is necessary to induce E2-dependent ERα-mediated appropriate physiologic responses in the uterus.
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
authors.forename: Daesuk
authors.initials: D
authors.lastname: Chung
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Alicia
authors.initials: A
authors.lastname: Ostmann
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Hou
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
mesh_terms: D000818:Animals; D001483:Base Sequence; D002466:Cell Nucleolus / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D010064:Embryo Implantation; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011247:Pregnancy; D016601:RNA-Binding Proteins; D011817:Rabbits; D020218:Response Elements; D015398:Signal Transduction; D015854:Up-Regulation; D014599:Uterus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D009363:Neoplasm Proteins; C438198:Nol5 protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D004958:Estradiol