Estrogen-dependent Transcription of the NEL-like 2 (NELL2) Gene and Its Role in Protection from Cell Death
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 t...
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| Veröffentlicht in: | The Journal of biological chemistry 2010-08, Vol.285 (32), p.25074-25084 |
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| creator | 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 R. Lee, Byung Ju |
| description | 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. |
| doi_str_mv | 10.1074/jbc.M110.100545 |
| format | Article |
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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.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M110.100545</identifier><identifier>PMID: 20538601</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; Cell Death ; DNA Primers - genetics ; Estrogen ; Estrogens - metabolism ; Gene Expression ; Gene Expression Regulation ; Gene Regulation ; Half-ERE ; Hippocampus - metabolism ; Mice ; Mitogen-Activated Protein Kinase 3 - metabolism ; Models, Biological ; NELL2 ; Nerve Tissue Proteins - metabolism ; Neurobiology ; Neuroprogenitor Cell ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Response Elements ; Signal Transduction ; Transcription Regulation</subject><ispartof>The Journal of biological chemistry, 2010-08, Vol.285 (32), p.25074-25084</ispartof><rights>2010 © 2010 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2010 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c564t-31dc0b44797d17305ec726ea4de0caa613a669fd677b4dbddeac89edff2c40df3</citedby><cites>FETCH-LOGICAL-c564t-31dc0b44797d17305ec726ea4de0caa613a669fd677b4dbddeac89edff2c40df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915743/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915743/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20538601$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Eun Jung</creatorcontrib><creatorcontrib>Kim, Dong Hee</creatorcontrib><creatorcontrib>Kim, Jae Geun</creatorcontrib><creatorcontrib>Kim, Dong Yeol</creatorcontrib><creatorcontrib>Kim, Jung Dae</creatorcontrib><creatorcontrib>Seol, Ok Ju</creatorcontrib><creatorcontrib>Jeong, Choon Soo</creatorcontrib><creatorcontrib>Park, Jeong Woo</creatorcontrib><creatorcontrib>Choi, Min Young</creatorcontrib><creatorcontrib>Kang, Sung Goo</creatorcontrib><creatorcontrib>Costa, Maria E.</creatorcontrib><creatorcontrib>Ojeda, Sergio R.</creatorcontrib><creatorcontrib>Lee, Byung Ju</creatorcontrib><title>Estrogen-dependent Transcription of the NEL-like 2 (NELL2) Gene and Its Role in Protection from Cell Death</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>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.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Death</subject><subject>DNA Primers - genetics</subject><subject>Estrogen</subject><subject>Estrogens - metabolism</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulation</subject><subject>Half-ERE</subject><subject>Hippocampus - metabolism</subject><subject>Mice</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Models, Biological</subject><subject>NELL2</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurobiology</subject><subject>Neuroprogenitor Cell</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Structure, Tertiary</subject><subject>Response Elements</subject><subject>Signal Transduction</subject><subject>Transcription Regulation</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9vFCEUx4mxsWv17E25VQ_TAgMDczEx61qbrD-ibeKNMPBml3UWtjDbxP9e2mkbPZjIBcj7vC983xehF5ScUCL56aazJ5_o7Y0ILh6hGSWqrmpBfzxGM0IYrVom1CF6mvOGlMVb-gQdMiJq1RA6Q5tFHlNcQagc7CA4CCO-SCZkm_xu9DHg2ONxDfjzYlkN_idghl-X85K9wWcQAJvg8PmY8bc4APYBf01xBHvb2ae4xXMYBvwezLh-hg56M2R4frcfocsPi4v5x2r55ex8_m5ZWdHwsaqps6TjXLbSUVkTAVayBgx3QKwxDa1N07S9a6TsuOucA2NVC67vmeXE9fURejvp7vbdFpwtlpIZ9C75rUm_dDRe_10Jfq1X8VqzlgrJ6yJwfCeQ4tUe8qi3PtviwwSI-6yl4Eoq2vwHyVUZfyPbQp5OpE0x5wT9w38o0TdR6hKlvolST1GWjpd_2njg77MrwKsJ6E3UZpV81pffWSkQqsrElCpEOxFQxn3tIelsPQQLzqeSkXbR__P536cNtv4</recordid><startdate>20100806</startdate><enddate>20100806</enddate><creator>Choi, Eun Jung</creator><creator>Kim, Dong Hee</creator><creator>Kim, Jae Geun</creator><creator>Kim, Dong Yeol</creator><creator>Kim, Jung Dae</creator><creator>Seol, Ok Ju</creator><creator>Jeong, Choon Soo</creator><creator>Park, Jeong Woo</creator><creator>Choi, Min Young</creator><creator>Kang, Sung Goo</creator><creator>Costa, Maria E.</creator><creator>Ojeda, Sergio R.</creator><creator>Lee, Byung Ju</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope><scope>5PM</scope></search><sort><creationdate>20100806</creationdate><title>Estrogen-dependent Transcription of the NEL-like 2 (NELL2) Gene and Its Role in Protection from Cell Death</title><author>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 R. ; Lee, Byung Ju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c564t-31dc0b44797d17305ec726ea4de0caa613a669fd677b4dbddeac89edff2c40df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Cell Death</topic><topic>DNA Primers - genetics</topic><topic>Estrogen</topic><topic>Estrogens - metabolism</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation</topic><topic>Gene Regulation</topic><topic>Half-ERE</topic><topic>Hippocampus - metabolism</topic><topic>Mice</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Models, Biological</topic><topic>NELL2</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Neurobiology</topic><topic>Neuroprogenitor Cell</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Structure, Tertiary</topic><topic>Response Elements</topic><topic>Signal Transduction</topic><topic>Transcription Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Eun Jung</creatorcontrib><creatorcontrib>Kim, Dong Hee</creatorcontrib><creatorcontrib>Kim, Jae Geun</creatorcontrib><creatorcontrib>Kim, Dong Yeol</creatorcontrib><creatorcontrib>Kim, Jung Dae</creatorcontrib><creatorcontrib>Seol, Ok Ju</creatorcontrib><creatorcontrib>Jeong, Choon Soo</creatorcontrib><creatorcontrib>Park, Jeong Woo</creatorcontrib><creatorcontrib>Choi, Min Young</creatorcontrib><creatorcontrib>Kang, Sung Goo</creatorcontrib><creatorcontrib>Costa, Maria E.</creatorcontrib><creatorcontrib>Ojeda, Sergio R.</creatorcontrib><creatorcontrib>Lee, Byung Ju</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Eun Jung</au><au>Kim, Dong Hee</au><au>Kim, Jae Geun</au><au>Kim, Dong Yeol</au><au>Kim, Jung Dae</au><au>Seol, Ok Ju</au><au>Jeong, Choon Soo</au><au>Park, Jeong Woo</au><au>Choi, Min Young</au><au>Kang, Sung Goo</au><au>Costa, Maria E.</au><au>Ojeda, Sergio R.</au><au>Lee, Byung Ju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogen-dependent Transcription of the NEL-like 2 (NELL2) Gene and Its Role in Protection from Cell Death</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2010-08-06</date><risdate>2010</risdate><volume>285</volume><issue>32</issue><spage>25074</spage><epage>25084</epage><pages>25074-25084</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20538601</pmid><doi>10.1074/jbc.M110.100545</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis Cell Death DNA Primers - genetics Estrogen Estrogens - metabolism Gene Expression Gene Expression Regulation Gene Regulation Half-ERE Hippocampus - metabolism Mice Mitogen-Activated Protein Kinase 3 - metabolism Models, Biological NELL2 Nerve Tissue Proteins - metabolism Neurobiology Neuroprogenitor Cell Promoter Regions, Genetic Protein Structure, Tertiary Response Elements Signal Transduction Transcription Regulation |
| title | Estrogen-dependent Transcription of the NEL-like 2 (NELL2) Gene and Its Role in Protection from Cell Death |
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