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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0027v1 198/3/489    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sakai, N. Articles by Sakurada, K. Search for Related Content PubMed PubMed Citation Articles by Sakai, N. Articles by Sakurada, K.

N Sakai, Bayer Yakuhin Ltd, Kobe, Japan
H Terami, Bayer Yakuhin Ltd, Kobe, Japan
S Suzuki, Japan
M Haga, Bayer Yakuhin Ltd, Kobe, Japan
K Nomoto, Bayer Yakuhin Ltd, Kobe, Japan
N Tsuchida, Bayer Yakuhin Ltd, Kobe, Japan
K Morohashi, National Institute for Basic Biology, Okazaki, Japan
N Saito, Biosignal Research Center, Kobe University, Kobe, Japan
M Asada, National Research Institute for Child Health and Development, Setagaya, Japan
M Hashimoto, National Research Institute for Child Health and Development, Setagaya, Japan
D Harada, National Research Institute for Child Health and Development, Setagaya, Japan
H Asahara, National Research Institute for Child Health and Development, Setagaya, Japan
T Ishikawa, Bayer Yakuhin Ltd, Kobe, Japan
F Shimada, Bayer Yakuhin Ltd, Kobe, Japan
K Sakurada, Bayer Yakuhin Ltd, Kobe, Japan

Correspondence: Shinobu Suzuki, Email: shinobu7{at}white.plala.or.jp

Abstract

Steroidogenic factor 1 (SF-1)/adrenal 4 binding protein (Ad4BP)/nuclear receptor subfamily 5, group A, member 1 (NR5A1), is a transcription factor involved in the development of adrenal/gonadal tissues and steroidogenic linage cell differentiation in adult somatic stem cells. To understand the cellular signaling network which regulates SF-1 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. SF-1 gene expression was activated in mesenchymal stem cells (MSCs) by siRNA directed against Protein kinase C (PKC) delta, erb-B3, RhoGAP (ARHGAP26) and hexokinase 2, none of which were previously known to be involved in SF-1 gene expression. Among these we identified crosstalk between erb-B3 and PKC delta signaling cascades. In addition, the gain of function studies indicated that SRY (sex determining region Y)-box 15 (SOX15), TEA domain family member 4 (TEAD-4), KIAA1257 (a gene of unknown function), ADAM metallopeptidase with thrombospondin type 1 motif 6 (ADAMTS6), Josephin domain containing 1 (JOSD1), centromere protein (CENP), TATA box binding protein (TBP)-associated factor 5-like RNA polymerase (TAF5) and inducible T-cell co-stimulator (ICOS) activate SF-1 gene expression. These results provide new insights into the molecular mechanisms of SF-1 gene expression.