Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death

Eun Jung Choi, Dong Hee Kim, Jae Geun Kim, Dong Yeol Kim, Jung Dae Kim, Ok Ju Seol, Choon Soo Jeong, Jeong Woo Park, Min Young Choi, Sung Goo Kang, Maria E. Costa, Sergio Ojeda, Byung Ju Lee

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays showed that E2 and its receptors (ERα and ERβ) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5 cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK.

    Original languageEnglish (US)
    Pages (from-to)25074-25084
    Number of pages11
    JournalJournal of Biological Chemistry
    Volume285
    Issue number32
    DOIs
    StatePublished - Aug 6 2010

    Fingerprint

    Response Elements
    Cell death
    Transcription
    Cell Survival
    Estrogens
    Cell Death
    Genes
    Cells
    Preoptic Area
    Mitogen-Activated Protein Kinase 3
    MAP Kinase Signaling System
    Mitogen-Activated Protein Kinase 1
    Assays
    Electrophoretic Mobility Shift Assay
    Epidermal Growth Factor
    Tissue
    Electrophoretic mobility
    Glycoproteins
    Phosphorylation
    Messenger RNA

    ASJC Scopus subject areas

    • Biochemistry
    • Cell Biology
    • Molecular Biology
    • Medicine(all)

    Cite this

    Choi, E. J., Kim, D. H., Kim, J. G., Kim, D. Y., Kim, J. D., Seol, O. J., ... Lee, B. J. (2010). Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death. Journal of Biological Chemistry, 285(32), 25074-25084. https://doi.org/10.1074/jbc.M110.100545

    Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death. / Choi, Eun Jung; Kim, Dong Hee; Kim, Jae Geun; Kim, Dong Yeol; Kim, Jung Dae; Seol, Ok Ju; Jeong, Choon Soo; Park, Jeong Woo; Choi, Min Young; Kang, Sung Goo; Costa, Maria E.; Ojeda, Sergio; Lee, Byung Ju.

    In: Journal of Biological Chemistry, Vol. 285, No. 32, 06.08.2010, p. 25074-25084.

    Research output: Contribution to journalArticle

    Choi, EJ, Kim, DH, Kim, JG, Kim, DY, Kim, JD, Seol, OJ, Jeong, CS, Park, JW, Choi, MY, Kang, SG, Costa, ME, Ojeda, S & Lee, BJ 2010, 'Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death', Journal of Biological Chemistry, vol. 285, no. 32, pp. 25074-25084. https://doi.org/10.1074/jbc.M110.100545
    Choi, Eun Jung ; Kim, Dong Hee ; Kim, Jae Geun ; Kim, Dong Yeol ; Kim, Jung Dae ; Seol, Ok Ju ; Jeong, Choon Soo ; Park, Jeong Woo ; Choi, Min Young ; Kang, Sung Goo ; Costa, Maria E. ; Ojeda, Sergio ; Lee, Byung Ju. / Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 32. pp. 25074-25084.
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    abstract = "NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays showed that E2 and its receptors (ERα and ERβ) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5 cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK.",
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    AU - Kim, Jung Dae

    AU - Seol, Ok Ju

    AU - Jeong, Choon Soo

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    AU - Choi, Min Young

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    AU - Costa, Maria E.

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