PMID- 27890615 OWN - NLM STAT- MEDLINE DCOM- 20170602 LR - 20180118 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 482 IP - 4 DP - 2017 Jan 22 TI - EGR2 is a gonadotropin-induced survival factor that controls the expression of IER3 in ovarian granulosa cells. PG - 877-882 LID - S0006-291X(16)32001-0 [pii] LID - 10.1016/j.bbrc.2016.11.127 [doi] AB - Pituitary gonadotropins are key hormones that orchestrate the growth and development of ovarian follicles. However, limited information is available on intra-ovarian factors that mediate the actions of gonadotropins. In this study, we identified that the early growth response 2 gene (EGR2) is a gonadotropin-inducible gene in granulosa cells of rats and humans. Analysis of consensus EGR-binding elements (EBEs) showed that the immediate early response 3 gene (IER3) is a novel transcriptional target gene of EGR2 as confirmed by the luciferase assay, electrophoretic mobility-shift assay (EMSA), chromatin immunoprecipitation (ChIP), and western blot analysis. Overexpression of EGR2 promoted survival of KGN human granulosa-derived cells in which IER3 acts as a mediator; knockdown of EGR2 induced death in KGN cells. Additionally, EGR2 was found to regulate the expression of myeloid cell leukemia 1 (MCL-1), which belongs to the BCL-2 family of proteins regulating cell survival. Thus, this study identified a novel signaling axis, comprised of gonadotropins-EGR2-IER3, which is important for the survival of granulosa cells during folliculogenesis. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Jin, Hanyong AU - Jin H AD - School of Pharmacy, Chung-Ang University, Seoul 06974, South Korea. FAU - Won, Miae AU - Won M AD - Department of Pharmacy, CHA University, Seongnam 13488, South Korea. FAU - Shin, Eunkyoung AU - Shin E AD - School of Pharmacy, Chung-Ang University, Seoul 06974, South Korea. FAU - Kim, Hong-Man AU - Kim HM AD - Department of Life Science, Chung-Ang University, Seoul 06974, South Korea. FAU - Lee, Kangseok AU - Lee K AD - Department of Life Science, Chung-Ang University, Seoul 06974, South Korea. FAU - Bae, Jeehyeon AU - Bae J AD - School of Pharmacy, Chung-Ang University, Seoul 06974, South Korea. Electronic address: jeehyeon@cau.ac.kr. LA - eng PT - Journal Article DEP - 20161124 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (EGR2 protein, human) RN - 0 (Early Growth Response Protein 2) RN - 0 (Egr2 protein, rat) RN - 0 (Gonadotropins) RN - 0 (IER3 protein, human) RN - 0 (IER3 protein, rat) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Apoptosis Regulatory Proteins/*genetics MH - Base Sequence MH - Cell Line MH - Cell Survival MH - Early Growth Response Protein 2/*genetics/metabolism MH - Female MH - Gonadotropins/*metabolism MH - Granulosa Cells/cytology/*metabolism MH - Humans MH - Membrane Proteins/*genetics MH - Promoter Regions, Genetic MH - RNA, Messenger/genetics MH - Rats MH - Rats, Sprague-Dawley MH - *Transcriptional Activation OTO - NOTNLM OT - FSH OT - KROX20 OT - LH OT - Target gene OT - Transcriptional regulation EDAT- 2016/11/29 06:00 MHDA- 2017/06/03 06:00 CRDT- 2016/11/29 06:00 PHST- 2016/11/10 00:00 [received] PHST- 2016/11/23 00:00 [accepted] PHST- 2016/11/29 06:00 [pubmed] PHST- 2017/06/03 06:00 [medline] PHST- 2016/11/29 06:00 [entrez] AID - S0006-291X(16)32001-0 [pii] AID - 10.1016/j.bbrc.2016.11.127 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2017 Jan 22;482(4):877-882. doi: 10.1016/j.bbrc.2016.11.127. Epub 2016 Nov 24.