Conserved MicroRNA miR-8/miR-200 and Its Target USH/FOG2 Control Growth by Regulating PI3K
How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fa...
Gespeichert in:
| Veröffentlicht in: | Cell 2009-12, Vol.139 (6), p.1096-1108 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1108 |
|---|---|
| container_issue | 6 |
| container_start_page | 1096 |
| container_title | Cell |
| container_volume | 139 |
| creator | Hyun, Seogang Lee, Jung Hyun Jin, Hua Nam, JinWu Namkoong, Bumjin Lee, Gina Chung, Jongkyeong Kim, V. Narry |
| description | How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85α, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer. |
| doi_str_mv | 10.1016/j.cell.2009.11.020 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_734191376</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0092867409014329</els_id><sourcerecordid>21173090</sourcerecordid><originalsourceid>FETCH-LOGICAL-c496t-908cd42101f335cff43abe557ccb574f0aeb7e69e50fbc495a6537a2bce5de9f3</originalsourceid><addsrcrecordid>eNp9kE9P2zAYhy00NArbF9hh8mmckr624ziRdkEVlIq_6uDCxXKcN52rNAE7BfHtcVTgyMU--Hl-kh9CfjFIGbB8uk4ttm3KAcqUsRQ47JEJg1IlGVP8G5nEB54UucoOyGEIawAopJTfyUFUQBYgJuRh1ncB_TPW9MpZ3y-vT-jGLZNiOp6Ro6ar6WII9M74FQ70_t_59OxmzmkUB9-3dO77l-E_rV7pElfb1gyuW9Hbhbj4QfYb0wb8-X4fkfuz07vZeXJ5M1_MTi4Tm5X5kJRQ2Drj8UeNENI2TSZMhVIqayupsgYMVgrzEiU0VVSkyaVQhlcWZY1lI47I8W730fdPWwyD3rgwljEd9tuglchYyYTKI_nnS5IzpgSUEEG-A2OREDw2-tG7jfGvmoEe2-u1Hj09tteM6dg-Sr_f17fVButP5SN2BP7uAIw1nh16HazDzmLtPNpB1737av8NcyaSZw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>21173090</pqid></control><display><type>article</type><title>Conserved MicroRNA miR-8/miR-200 and Its Target USH/FOG2 Control Growth by Regulating PI3K</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>ScienceDirect Journals (5 years ago - present)</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Hyun, Seogang ; Lee, Jung Hyun ; Jin, Hua ; Nam, JinWu ; Namkoong, Bumjin ; Lee, Gina ; Chung, Jongkyeong ; Kim, V. Narry</creator><creatorcontrib>Hyun, Seogang ; Lee, Jung Hyun ; Jin, Hua ; Nam, JinWu ; Namkoong, Bumjin ; Lee, Gina ; Chung, Jongkyeong ; Kim, V. Narry</creatorcontrib><description>How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85α, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2009.11.020</identifier><identifier>PMID: 20005803</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adipose Tissue - metabolism ; Animals ; Body Size ; DNA-Binding Proteins - metabolism ; Drosophila ; Drosophila melanogaster - genetics ; Drosophila melanogaster - physiology ; Drosophila Proteins ; Humans ; HUMDISEASE ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Mutation ; Phosphatidylinositol 3-Kinases - metabolism ; RNA ; SIGNALING ; Transcription Factors - metabolism</subject><ispartof>Cell, 2009-12, Vol.139 (6), p.1096-1108</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-908cd42101f335cff43abe557ccb574f0aeb7e69e50fbc495a6537a2bce5de9f3</citedby><cites>FETCH-LOGICAL-c496t-908cd42101f335cff43abe557ccb574f0aeb7e69e50fbc495a6537a2bce5de9f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cell.2009.11.020$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20005803$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hyun, Seogang</creatorcontrib><creatorcontrib>Lee, Jung Hyun</creatorcontrib><creatorcontrib>Jin, Hua</creatorcontrib><creatorcontrib>Nam, JinWu</creatorcontrib><creatorcontrib>Namkoong, Bumjin</creatorcontrib><creatorcontrib>Lee, Gina</creatorcontrib><creatorcontrib>Chung, Jongkyeong</creatorcontrib><creatorcontrib>Kim, V. Narry</creatorcontrib><title>Conserved MicroRNA miR-8/miR-200 and Its Target USH/FOG2 Control Growth by Regulating PI3K</title><title>Cell</title><addtitle>Cell</addtitle><description>How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85α, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer.</description><subject>Adipose Tissue - metabolism</subject><subject>Animals</subject><subject>Body Size</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drosophila</subject><subject>Drosophila melanogaster - genetics</subject><subject>Drosophila melanogaster - physiology</subject><subject>Drosophila Proteins</subject><subject>Humans</subject><subject>HUMDISEASE</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Mutation</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>RNA</subject><subject>SIGNALING</subject><subject>Transcription Factors - metabolism</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9P2zAYhy00NArbF9hh8mmckr624ziRdkEVlIq_6uDCxXKcN52rNAE7BfHtcVTgyMU--Hl-kh9CfjFIGbB8uk4ttm3KAcqUsRQ47JEJg1IlGVP8G5nEB54UucoOyGEIawAopJTfyUFUQBYgJuRh1ncB_TPW9MpZ3y-vT-jGLZNiOp6Ro6ar6WII9M74FQ70_t_59OxmzmkUB9-3dO77l-E_rV7pElfb1gyuW9Hbhbj4QfYb0wb8-X4fkfuz07vZeXJ5M1_MTi4Tm5X5kJRQ2Drj8UeNENI2TSZMhVIqayupsgYMVgrzEiU0VVSkyaVQhlcWZY1lI47I8W730fdPWwyD3rgwljEd9tuglchYyYTKI_nnS5IzpgSUEEG-A2OREDw2-tG7jfGvmoEe2-u1Hj09tteM6dg-Sr_f17fVButP5SN2BP7uAIw1nh16HazDzmLtPNpB1737av8NcyaSZw</recordid><startdate>20091211</startdate><enddate>20091211</enddate><creator>Hyun, Seogang</creator><creator>Lee, Jung Hyun</creator><creator>Jin, Hua</creator><creator>Nam, JinWu</creator><creator>Namkoong, Bumjin</creator><creator>Lee, Gina</creator><creator>Chung, Jongkyeong</creator><creator>Kim, V. Narry</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20091211</creationdate><title>Conserved MicroRNA miR-8/miR-200 and Its Target USH/FOG2 Control Growth by Regulating PI3K</title><author>Hyun, Seogang ; Lee, Jung Hyun ; Jin, Hua ; Nam, JinWu ; Namkoong, Bumjin ; Lee, Gina ; Chung, Jongkyeong ; Kim, V. Narry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-908cd42101f335cff43abe557ccb574f0aeb7e69e50fbc495a6537a2bce5de9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adipose Tissue - metabolism</topic><topic>Animals</topic><topic>Body Size</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Drosophila</topic><topic>Drosophila melanogaster - genetics</topic><topic>Drosophila melanogaster - physiology</topic><topic>Drosophila Proteins</topic><topic>Humans</topic><topic>HUMDISEASE</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Mutation</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>RNA</topic><topic>SIGNALING</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hyun, Seogang</creatorcontrib><creatorcontrib>Lee, Jung Hyun</creatorcontrib><creatorcontrib>Jin, Hua</creatorcontrib><creatorcontrib>Nam, JinWu</creatorcontrib><creatorcontrib>Namkoong, Bumjin</creatorcontrib><creatorcontrib>Lee, Gina</creatorcontrib><creatorcontrib>Chung, Jongkyeong</creatorcontrib><creatorcontrib>Kim, V. Narry</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hyun, Seogang</au><au>Lee, Jung Hyun</au><au>Jin, Hua</au><au>Nam, JinWu</au><au>Namkoong, Bumjin</au><au>Lee, Gina</au><au>Chung, Jongkyeong</au><au>Kim, V. Narry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conserved MicroRNA miR-8/miR-200 and Its Target USH/FOG2 Control Growth by Regulating PI3K</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2009-12-11</date><risdate>2009</risdate><volume>139</volume><issue>6</issue><spage>1096</spage><epage>1108</epage><pages>1096-1108</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85α, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20005803</pmid><doi>10.1016/j.cell.2009.11.020</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0092-8674 |
| ispartof | Cell, 2009-12, Vol.139 (6), p.1096-1108 |
| issn | 0092-8674 1097-4172 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_734191376 |
| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | Adipose Tissue - metabolism Animals Body Size DNA-Binding Proteins - metabolism Drosophila Drosophila melanogaster - genetics Drosophila melanogaster - physiology Drosophila Proteins Humans HUMDISEASE MicroRNAs - genetics MicroRNAs - metabolism Mutation Phosphatidylinositol 3-Kinases - metabolism RNA SIGNALING Transcription Factors - metabolism |
| title | Conserved MicroRNA miR-8/miR-200 and Its Target USH/FOG2 Control Growth by Regulating PI3K |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T05%3A26%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Conserved%20MicroRNA%20miR-8/miR-200%20and%20Its%20Target%20USH/FOG2%20Control%20Growth%20by%20Regulating%20PI3K&rft.jtitle=Cell&rft.au=Hyun,%20Seogang&rft.date=2009-12-11&rft.volume=139&rft.issue=6&rft.spage=1096&rft.epage=1108&rft.pages=1096-1108&rft.issn=0092-8674&rft.eissn=1097-4172&rft_id=info:doi/10.1016/j.cell.2009.11.020&rft_dat=%3Cproquest_cross%3E21173090%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=21173090&rft_id=info:pmid/20005803&rft_els_id=S0092867409014329&rfr_iscdi=true |