Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression
We previously reported an intricate mechanism underlying the homeostasis of Oct4 expression in normally proliferating stem cell culture of P19, mediated by SUMOylation of orphan nuclear receptor TR2. In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-08, Vol.105 (32), p.11424-11429 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 11429 |
|---|---|
| container_issue | 32 |
| container_start_page | 11424 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 105 |
| creator | Gupta, Pawan Ho, Ping-Chih Huq, MD Mostaqul Ha, Sung Gil Park, Sung Wook Khan, Amjad Ali Tsai, Nien-Pei Wei, Li-Na |
| description | We previously reported an intricate mechanism underlying the homeostasis of Oct4 expression in normally proliferating stem cell culture of P19, mediated by SUMOylation of orphan nuclear receptor TR2. In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). The activated ERK2 phosphorylates threonine-210 (Thr-210) of TR2, stimulating its subsequent SUMOylation. Dephosphorylated TR2 recruits coactivator PCAF and functions as an activator for its target gene Oct4. Upon phosphorylation at Thr-210, TR2 increasingly associates with promyelocytic leukemia (PML) nuclear bodies, becomes SUMOylated, and recruits corepressor RIP140 to act as a repressor for its target, Oct4. To normally proliferating P19 stem cell culture, exposure to a physiological concentration of atRA triggers a rapid nongenomic signaling cascade to suppress Oct4 gene and regulate cell proliferation. |
| doi_str_mv | 10.1073/pnas.0710561105 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1073_pnas_0710561105</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>25463354</jstor_id><sourcerecordid>25463354</sourcerecordid><originalsourceid>FETCH-LOGICAL-c593t-1f292401f98723dd1d8601b388c76a7d4330bd7801265ad8bc24912d2b210dbd3</originalsourceid><addsrcrecordid>eNqFkktv1DAUhS0EosPAmhXgFRJS0_oRO84GCVW8pKkGtZ215dhO6yqJU9tB7U_gX-MwUQdWLGzLOt8998rHALzG6ASjip6Og4onqMKIcZy3J2CFUY0LXtboKVghRKpClKQ8Ai9ivEUI1Uyg5-AICy4IY3QFfl3Y5AbvNFTamSIm10-dStbAaO8mOySnOjje-JhXeMiK88Mx_HG-gcHqMLnUZ-YYqsHAy935diGgb-Ew6c6qMHN2TD7AqwsCk4dxGsdgY4RbnUpo7_9ccs1L8KxVXbSvlnMNdl8-X519Kzbbr9_PPm0KzWqaCtySmpQIt7WoCDUGG8ERbqgQuuKqMiWlqDGVQJhwpoxoNClrTAxpCEamMXQNPu59x6nprdF5_qA6OQbXq_AgvXLyX2VwN_La_5SEYU6y_Rq8XwyCz08Uk-xd1Lbr1GD9FCVBQtSU8wye7kEdfIzBto9NMJJzfHKOTx7iyxVv_57twC95ZeDDAsyVBzsmKZEY56hlO3Vdsvcps_A_bEbe7JHbmBN6ZAgrOaVs1t_t9VZ5qa6Di3J3SRCm-ScRJmhNfwNwx8Se</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20889366</pqid></control><display><type>article</type><title>Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Gupta, Pawan ; Ho, Ping-Chih ; Huq, MD Mostaqul ; Ha, Sung Gil ; Park, Sung Wook ; Khan, Amjad Ali ; Tsai, Nien-Pei ; Wei, Li-Na</creator><creatorcontrib>Gupta, Pawan ; Ho, Ping-Chih ; Huq, MD Mostaqul ; Ha, Sung Gil ; Park, Sung Wook ; Khan, Amjad Ali ; Tsai, Nien-Pei ; Wei, Li-Na</creatorcontrib><description>We previously reported an intricate mechanism underlying the homeostasis of Oct4 expression in normally proliferating stem cell culture of P19, mediated by SUMOylation of orphan nuclear receptor TR2. In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). The activated ERK2 phosphorylates threonine-210 (Thr-210) of TR2, stimulating its subsequent SUMOylation. Dephosphorylated TR2 recruits coactivator PCAF and functions as an activator for its target gene Oct4. Upon phosphorylation at Thr-210, TR2 increasingly associates with promyelocytic leukemia (PML) nuclear bodies, becomes SUMOylated, and recruits corepressor RIP140 to act as a repressor for its target, Oct4. To normally proliferating P19 stem cell culture, exposure to a physiological concentration of atRA triggers a rapid nongenomic signaling cascade to suppress Oct4 gene and regulate cell proliferation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0710561105</identifier><identifier>PMID: 18682553</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Actins ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Antineoplastic Agents - pharmacology ; Biological Sciences ; Cell Line ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Gene expression regulation ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - physiology ; Genes ; Genomics ; Homeostasis - drug effects ; Homeostasis - physiology ; MAP Kinase Kinase Kinases - metabolism ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; Mice ; Mitogen-Activated Protein Kinase 1 - metabolism ; Nuclear Proteins - metabolism ; Nuclear Receptor Interacting Protein 1 ; Nuclear Receptor Subfamily 2, Group C, Member 1 ; Octamer Transcription Factor-3 - biosynthesis ; Orphans ; p300-CBP Transcription Factors - metabolism ; Phosphorylation ; Phosphorylation - drug effects ; Pluripotent stem cells ; Promyelocytic Leukemia Protein ; Receptors ; Receptors, Thyroid Hormone - metabolism ; Repressor Proteins - metabolism ; Stem cells ; SUMO-1 Protein - metabolism ; Transcription Factors - metabolism ; Tretinoin - pharmacology ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-08, Vol.105 (32), p.11424-11429</ispartof><rights>Copyright 2008 The National Academy of Sciences of the United States of America</rights><rights>2008 by The National Academy of Sciences of the USA</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-1f292401f98723dd1d8601b388c76a7d4330bd7801265ad8bc24912d2b210dbd3</citedby><cites>FETCH-LOGICAL-c593t-1f292401f98723dd1d8601b388c76a7d4330bd7801265ad8bc24912d2b210dbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/32.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25463354$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25463354$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18682553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gupta, Pawan</creatorcontrib><creatorcontrib>Ho, Ping-Chih</creatorcontrib><creatorcontrib>Huq, MD Mostaqul</creatorcontrib><creatorcontrib>Ha, Sung Gil</creatorcontrib><creatorcontrib>Park, Sung Wook</creatorcontrib><creatorcontrib>Khan, Amjad Ali</creatorcontrib><creatorcontrib>Tsai, Nien-Pei</creatorcontrib><creatorcontrib>Wei, Li-Na</creatorcontrib><title>Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We previously reported an intricate mechanism underlying the homeostasis of Oct4 expression in normally proliferating stem cell culture of P19, mediated by SUMOylation of orphan nuclear receptor TR2. In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). The activated ERK2 phosphorylates threonine-210 (Thr-210) of TR2, stimulating its subsequent SUMOylation. Dephosphorylated TR2 recruits coactivator PCAF and functions as an activator for its target gene Oct4. Upon phosphorylation at Thr-210, TR2 increasingly associates with promyelocytic leukemia (PML) nuclear bodies, becomes SUMOylated, and recruits corepressor RIP140 to act as a repressor for its target, Oct4. To normally proliferating P19 stem cell culture, exposure to a physiological concentration of atRA triggers a rapid nongenomic signaling cascade to suppress Oct4 gene and regulate cell proliferation.</description><subject>Actins</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological Sciences</subject><subject>Cell Line</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Gene expression regulation</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - physiology</subject><subject>Genes</subject><subject>Genomics</subject><subject>Homeostasis - drug effects</subject><subject>Homeostasis - physiology</subject><subject>MAP Kinase Kinase Kinases - metabolism</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Mice</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nuclear Receptor Interacting Protein 1</subject><subject>Nuclear Receptor Subfamily 2, Group C, Member 1</subject><subject>Octamer Transcription Factor-3 - biosynthesis</subject><subject>Orphans</subject><subject>p300-CBP Transcription Factors - metabolism</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Pluripotent stem cells</subject><subject>Promyelocytic Leukemia Protein</subject><subject>Receptors</subject><subject>Receptors, Thyroid Hormone - metabolism</subject><subject>Repressor Proteins - metabolism</subject><subject>Stem cells</subject><subject>SUMO-1 Protein - metabolism</subject><subject>Transcription Factors - metabolism</subject><subject>Tretinoin - pharmacology</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAUhS0EosPAmhXgFRJS0_oRO84GCVW8pKkGtZ215dhO6yqJU9tB7U_gX-MwUQdWLGzLOt8998rHALzG6ASjip6Og4onqMKIcZy3J2CFUY0LXtboKVghRKpClKQ8Ai9ivEUI1Uyg5-AICy4IY3QFfl3Y5AbvNFTamSIm10-dStbAaO8mOySnOjje-JhXeMiK88Mx_HG-gcHqMLnUZ-YYqsHAy935diGgb-Ew6c6qMHN2TD7AqwsCk4dxGsdgY4RbnUpo7_9ccs1L8KxVXbSvlnMNdl8-X519Kzbbr9_PPm0KzWqaCtySmpQIt7WoCDUGG8ERbqgQuuKqMiWlqDGVQJhwpoxoNClrTAxpCEamMXQNPu59x6nprdF5_qA6OQbXq_AgvXLyX2VwN_La_5SEYU6y_Rq8XwyCz08Uk-xd1Lbr1GD9FCVBQtSU8wye7kEdfIzBto9NMJJzfHKOTx7iyxVv_57twC95ZeDDAsyVBzsmKZEY56hlO3Vdsvcps_A_bEbe7JHbmBN6ZAgrOaVs1t_t9VZ5qa6Di3J3SRCm-ScRJmhNfwNwx8Se</recordid><startdate>20080812</startdate><enddate>20080812</enddate><creator>Gupta, Pawan</creator><creator>Ho, Ping-Chih</creator><creator>Huq, MD Mostaqul</creator><creator>Ha, Sung Gil</creator><creator>Park, Sung Wook</creator><creator>Khan, Amjad Ali</creator><creator>Tsai, Nien-Pei</creator><creator>Wei, Li-Na</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20080812</creationdate><title>Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression</title><author>Gupta, Pawan ; Ho, Ping-Chih ; Huq, MD Mostaqul ; Ha, Sung Gil ; Park, Sung Wook ; Khan, Amjad Ali ; Tsai, Nien-Pei ; Wei, Li-Na</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-1f292401f98723dd1d8601b388c76a7d4330bd7801265ad8bc24912d2b210dbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Actins</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological Sciences</topic><topic>Cell Line</topic><topic>Embryonic stem cells</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Gene expression regulation</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - physiology</topic><topic>Genes</topic><topic>Genomics</topic><topic>Homeostasis - drug effects</topic><topic>Homeostasis - physiology</topic><topic>MAP Kinase Kinase Kinases - metabolism</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Mice</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nuclear Receptor Interacting Protein 1</topic><topic>Nuclear Receptor Subfamily 2, Group C, Member 1</topic><topic>Octamer Transcription Factor-3 - biosynthesis</topic><topic>Orphans</topic><topic>p300-CBP Transcription Factors - metabolism</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Pluripotent stem cells</topic><topic>Promyelocytic Leukemia Protein</topic><topic>Receptors</topic><topic>Receptors, Thyroid Hormone - metabolism</topic><topic>Repressor Proteins - metabolism</topic><topic>Stem cells</topic><topic>SUMO-1 Protein - metabolism</topic><topic>Transcription Factors - metabolism</topic><topic>Tretinoin - pharmacology</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gupta, Pawan</creatorcontrib><creatorcontrib>Ho, Ping-Chih</creatorcontrib><creatorcontrib>Huq, MD Mostaqul</creatorcontrib><creatorcontrib>Ha, Sung Gil</creatorcontrib><creatorcontrib>Park, Sung Wook</creatorcontrib><creatorcontrib>Khan, Amjad Ali</creatorcontrib><creatorcontrib>Tsai, Nien-Pei</creatorcontrib><creatorcontrib>Wei, Li-Na</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gupta, Pawan</au><au>Ho, Ping-Chih</au><au>Huq, MD Mostaqul</au><au>Ha, Sung Gil</au><au>Park, Sung Wook</au><au>Khan, Amjad Ali</au><au>Tsai, Nien-Pei</au><au>Wei, Li-Na</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2008-08-12</date><risdate>2008</risdate><volume>105</volume><issue>32</issue><spage>11424</spage><epage>11429</epage><pages>11424-11429</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>We previously reported an intricate mechanism underlying the homeostasis of Oct4 expression in normally proliferating stem cell culture of P19, mediated by SUMOylation of orphan nuclear receptor TR2. In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). The activated ERK2 phosphorylates threonine-210 (Thr-210) of TR2, stimulating its subsequent SUMOylation. Dephosphorylated TR2 recruits coactivator PCAF and functions as an activator for its target gene Oct4. Upon phosphorylation at Thr-210, TR2 increasingly associates with promyelocytic leukemia (PML) nuclear bodies, becomes SUMOylated, and recruits corepressor RIP140 to act as a repressor for its target, Oct4. To normally proliferating P19 stem cell culture, exposure to a physiological concentration of atRA triggers a rapid nongenomic signaling cascade to suppress Oct4 gene and regulate cell proliferation.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>18682553</pmid><doi>10.1073/pnas.0710561105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2008-08, Vol.105 (32), p.11424-11429 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_crossref_primary_10_1073_pnas_0710561105 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Actins Adaptor Proteins, Signal Transducing - metabolism Animals Antineoplastic Agents - pharmacology Biological Sciences Cell Line Embryonic stem cells Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Gene expression regulation Gene Expression Regulation - drug effects Gene Expression Regulation - physiology Genes Genomics Homeostasis - drug effects Homeostasis - physiology MAP Kinase Kinase Kinases - metabolism MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology Mice Mitogen-Activated Protein Kinase 1 - metabolism Nuclear Proteins - metabolism Nuclear Receptor Interacting Protein 1 Nuclear Receptor Subfamily 2, Group C, Member 1 Octamer Transcription Factor-3 - biosynthesis Orphans p300-CBP Transcription Factors - metabolism Phosphorylation Phosphorylation - drug effects Pluripotent stem cells Promyelocytic Leukemia Protein Receptors Receptors, Thyroid Hormone - metabolism Repressor Proteins - metabolism Stem cells SUMO-1 Protein - metabolism Transcription Factors - metabolism Tretinoin - pharmacology Tumor Suppressor Proteins - metabolism |
| title | Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T16%3A41%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Retinoic%20acid-stimulated%20sequential%20phosphorylation,%20PML%20recruitment,%20and%20SUMOylation%20of%20nuclear%20receptor%20TR2%20to%20suppress%20Oct4%20expression&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Gupta,%20Pawan&rft.date=2008-08-12&rft.volume=105&rft.issue=32&rft.spage=11424&rft.epage=11429&rft.pages=11424-11429&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.0710561105&rft_dat=%3Cjstor_cross%3E25463354%3C/jstor_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=20889366&rft_id=info:pmid/18682553&rft_jstor_id=25463354&rfr_iscdi=true |