Identification of NR5A1 (SF-1/AD4BP) gene expression modulators by large-scale gain and loss of function studies

Noriko Sakai, Hiromi Terami, Shinobu Suzuki, Megumi Haga, Ken Nomoto, Nobuko Tsuchida, Ken Ichirou Morohashi, Naoaki Saito, Maki Asada, Megumi Hashimoto, Daisuke Harada, Hiroshi Asahara, Tetsuya Ishikawa, Fumiki Shimada, Kazuhiro Sakurada

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6 Citations (Scopus)

Abstract

Nuclear receptor subfamily 5, group A, member 1 (NR5A1 previously known as SF-1/AD4BP) is a transcription factor involved in the development of adrenal/gonadal tissues and steroidogenic linage cell diffierentiation in adult somatic stem cells. To understand the cellular signaling network that regulates NR5A1 gene expression, loss of function screening with an siRNA kinome library, and gain of function screening with an addressable full-length cDNA library representing one quarter of the human genome was carried out. The NR5A1 gene expression was activated in mesenchymal stem cells by siRNA directed against protein kinase C (PKC)-δ, erb-B3, RhoGAP (ARHGAP26), and hexokinase 2, none of which were previously known to be involved in the NR5A1 gene expression. Among these, we identified crosstalk between erb-B3 and PKC-δ signaling cascades. In addition, the gain of function studies indicated that sex-determining region Y (SRY)-box 15 (SOX15), TEA domain family member 4, KIAA1257 (a gene of unknown function), ADAM metallopeptidase with thrombospondin type 1 motif 6, Josephin domain containing 1, centromere protein, TATA box-binding protein-associated factor 5-like RNA polymerase, and inducible T-cell co-stimulator activate NR5A1 gene expression. These results provide new insights into the molecular mechanisms of NR5A1 gene expression.

Original languageEnglish
Pages (from-to)489-497
Number of pages9
JournalJournal of Endocrinology
Volume198
Issue number3
DOIs
Publication statusPublished - Sep 1 2008

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Sakai, N., Terami, H., Suzuki, S., Haga, M., Nomoto, K., Tsuchida, N., ... Sakurada, K. (2008). Identification of NR5A1 (SF-1/AD4BP) gene expression modulators by large-scale gain and loss of function studies. Journal of Endocrinology, 198(3), 489-497. https://doi.org/10.1677/JOE-08-0027