NFκB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions
The transcription factor NFκB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. Additionally, posttranslational modification of the NFκB p65 subunit by O-linked N-acetylglucosamine (O-GlcNAc) has been reported, but the modific...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-11, Vol.105 (45), p.17345-17350 |
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| container_end_page | 17350 |
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| container_issue | 45 |
| container_start_page | 17345 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 105 |
| creator | Yang, Won Ho Park, Sang Yoon Nam, Hyung Wook Kim, Do Hyun Kang, Jeong Gu Kang, Eun Seok Kim, Yu Sam Lee, Hyun Chul Kim, Kwan Soo Cho, Jin Won |
| description | The transcription factor NFκB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. Additionally, posttranslational modification of the NFκB p65 subunit by O-linked N-acetylglucosamine (O-GlcNAc) has been reported, but the modification site of O-GlcNAc on NFκB p65 and its exact function have not been elucidated. In this work, we show that O-GlcNAcylation of NFκB p65 decreases binding to IκBα and increases transcriptional activity under hyperglycemic conditions. Also, we demonstrate that both Thr-322 and Thr-352 of NFκB p65 can be modified with O-GlcNAc, but modification on Thr-352, not Thr-322, is important for transcriptional activation. Our findings suggest that site-specific O-GlcNAcylation may be a reason why NFκB activity increases continuously under hyperglycemic conditions. |
| doi_str_mv | 10.1073/pnas.0806198105 |
| format | Article |
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Additionally, posttranslational modification of the NFκB p65 subunit by O-linked N-acetylglucosamine (O-GlcNAc) has been reported, but the modification site of O-GlcNAc on NFκB p65 and its exact function have not been elucidated. In this work, we show that O-GlcNAcylation of NFκB p65 decreases binding to IκBα and increases transcriptional activity under hyperglycemic conditions. Also, we demonstrate that both Thr-322 and Thr-352 of NFκB p65 can be modified with O-GlcNAc, but modification on Thr-352, not Thr-322, is important for transcriptional activation. Our findings suggest that site-specific O-GlcNAcylation may be a reason why NFκB activity increases continuously under hyperglycemic conditions.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0806198105</identifier><identifier>PMID: 18988733</identifier><language>eng</language><publisher>National Academy of Sciences</publisher><subject>Actins ; Antibodies ; Biological Sciences ; Cellular immunity ; Diabetes complications ; Gene expression regulation ; Immunoblotting ; Phosphorylation ; Plasmids ; Transcriptional activation ; Type 1 diabetes mellitus</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-11, Vol.105 (45), p.17345-17350</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-c442t-f174e8c0f9750b8d040a534c9e880fc4dd88e4fee43b0ecc0310a1ee0ae006bf3</citedby><cites>FETCH-LOGICAL-c442t-f174e8c0f9750b8d040a534c9e880fc4dd88e4fee43b0ecc0310a1ee0ae006bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/45.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25465280$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25465280$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27926,27927,53793,53795,58019,58252</link.rule.ids></links><search><creatorcontrib>Yang, Won Ho</creatorcontrib><creatorcontrib>Park, Sang Yoon</creatorcontrib><creatorcontrib>Nam, Hyung Wook</creatorcontrib><creatorcontrib>Kim, Do Hyun</creatorcontrib><creatorcontrib>Kang, Jeong Gu</creatorcontrib><creatorcontrib>Kang, Eun Seok</creatorcontrib><creatorcontrib>Kim, Yu Sam</creatorcontrib><creatorcontrib>Lee, Hyun Chul</creatorcontrib><creatorcontrib>Kim, Kwan Soo</creatorcontrib><creatorcontrib>Cho, Jin Won</creatorcontrib><title>NFκB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions</title><title>Proceedings of the National Academy of Sciences - PNAS</title><description>The transcription factor NFκB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. 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Our findings suggest that site-specific O-GlcNAcylation may be a reason why NFκB activity increases continuously under hyperglycemic conditions.</description><subject>Actins</subject><subject>Antibodies</subject><subject>Biological Sciences</subject><subject>Cellular immunity</subject><subject>Diabetes complications</subject><subject>Gene expression regulation</subject><subject>Immunoblotting</subject><subject>Phosphorylation</subject><subject>Plasmids</subject><subject>Transcriptional activation</subject><subject>Type 1 diabetes mellitus</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqFkT1vFDEQhi1ERI5ATYVwS7HJ-Ot2tkEKEQlIUVIk6ZAsn3d852hv92T7AvfX-BH8Jva0USKqNOPieeYd6TVjHwQcC6jVyaZ3-RgQ5qJBAeYVmwloRDXXDbxmMwBZV6ilPmRvc74HgMYgvGGHAhvEWqkZ-3l1_vfPV-58iQ-uxKHnMXOX8-CjK9TyX7GseCyZX1cXnb869btu0nIZOd_2LSW-2m0oLbudp3X03A99G_dOfscOgusyvX98j9jd-bfbs-_V5fXFj7PTy8prLUsVRK0JPYSmNrDAFjQ4o7RvCBGC122LSDoQabUA8h6UACeIwBHAfBHUEfsy5W62izW1nvqSXGc3Ka5d2tnBRfs_6ePKLocHKw1KiTgGnEwBPg05JwpPuwLsvmi7L9o-Fz1ufH48uQfPtrHaWFGrcYZt1xX6XUaXv-COysdJuc9lSE-ONHpuJMLIP008uMG6ZYrZ3t1IEAqEMY0Y__IfymGfDw</recordid><startdate>20081111</startdate><enddate>20081111</enddate><creator>Yang, Won Ho</creator><creator>Park, Sang Yoon</creator><creator>Nam, Hyung Wook</creator><creator>Kim, Do Hyun</creator><creator>Kang, Jeong Gu</creator><creator>Kang, Eun Seok</creator><creator>Kim, Yu Sam</creator><creator>Lee, Hyun Chul</creator><creator>Kim, Kwan Soo</creator><creator>Cho, Jin Won</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20081111</creationdate><title>NFκB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions</title><author>Yang, Won Ho ; Park, Sang Yoon ; Nam, Hyung Wook ; Kim, Do Hyun ; Kang, Jeong Gu ; Kang, Eun Seok ; Kim, Yu Sam ; Lee, Hyun Chul ; Kim, Kwan Soo ; Cho, Jin Won</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-f174e8c0f9750b8d040a534c9e880fc4dd88e4fee43b0ecc0310a1ee0ae006bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Actins</topic><topic>Antibodies</topic><topic>Biological Sciences</topic><topic>Cellular immunity</topic><topic>Diabetes complications</topic><topic>Gene expression regulation</topic><topic>Immunoblotting</topic><topic>Phosphorylation</topic><topic>Plasmids</topic><topic>Transcriptional activation</topic><topic>Type 1 diabetes mellitus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Won Ho</creatorcontrib><creatorcontrib>Park, Sang Yoon</creatorcontrib><creatorcontrib>Nam, Hyung Wook</creatorcontrib><creatorcontrib>Kim, Do Hyun</creatorcontrib><creatorcontrib>Kang, Jeong Gu</creatorcontrib><creatorcontrib>Kang, Eun Seok</creatorcontrib><creatorcontrib>Kim, Yu Sam</creatorcontrib><creatorcontrib>Lee, Hyun Chul</creatorcontrib><creatorcontrib>Kim, Kwan Soo</creatorcontrib><creatorcontrib>Cho, Jin Won</creatorcontrib><collection>AGRIS</collection><collection>CrossRef</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>Yang, Won Ho</au><au>Park, Sang Yoon</au><au>Nam, Hyung Wook</au><au>Kim, Do Hyun</au><au>Kang, Jeong Gu</au><au>Kang, Eun Seok</au><au>Kim, Yu Sam</au><au>Lee, Hyun Chul</au><au>Kim, Kwan Soo</au><au>Cho, Jin Won</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NFκB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><date>2008-11-11</date><risdate>2008</risdate><volume>105</volume><issue>45</issue><spage>17345</spage><epage>17350</epage><pages>17345-17350</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The transcription factor NFκB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. 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| source | PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; JSTOR |
| subjects | Actins Antibodies Biological Sciences Cellular immunity Diabetes complications Gene expression regulation Immunoblotting Phosphorylation Plasmids Transcriptional activation Type 1 diabetes mellitus |
| title | NFκB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions |
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