Involvement of the IRE1α-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases
The X-box binding protein 1 (XBP1) is not only an important component of the unfolded protein response (UPR), but also an important nuclear transcription factor. Upon endoplasmic reticulum stress, XBP1 is spliced by inositol-requiring enzyme 1 (IRE1), thereby generating functional spliced XBP1 (XBP1...
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| Veröffentlicht in: | DNA and cell biology 2015-01, Vol.34 (1), p.6-18 |
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| creator | Wu, Rong Zhang, Qing-Hai Lu, Yan-Ju Ren, Kun Yi, Guang-Hui |
| description | The X-box binding protein 1 (XBP1) is not only an important component of the unfolded protein response (UPR), but also an important nuclear transcription factor. Upon endoplasmic reticulum stress, XBP1 is spliced by inositol-requiring enzyme 1 (IRE1), thereby generating functional spliced XBP1 (XBP1s). XBP1s functions by translocating into the nucleus to initiate transcriptional programs that regulate a subset of UPR- and non-UPR-associated genes involved in the pathophysiological processes of various diseases. Recent reports have implicated XBP1 in metabolic diseases. This review summarizes the effects of XBP1-mediated regulation on lipid metabolism, glucose metabolism, obesity, and atherosclerosis. Additionally, for the first time, we present XBP1s-dependent transcriptional reprogramming in metabolic diseases under different conditions, including pathology and physiology. Understanding the function of XBP1 in metabolic diseases may provide a basic knowledge for the development of novel therapeutic targets for ameliorating these diseases. |
| doi_str_mv | 10.1089/dna.2014.2552 |
| format | Article |
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Upon endoplasmic reticulum stress, XBP1 is spliced by inositol-requiring enzyme 1 (IRE1), thereby generating functional spliced XBP1 (XBP1s). XBP1s functions by translocating into the nucleus to initiate transcriptional programs that regulate a subset of UPR- and non-UPR-associated genes involved in the pathophysiological processes of various diseases. Recent reports have implicated XBP1 in metabolic diseases. This review summarizes the effects of XBP1-mediated regulation on lipid metabolism, glucose metabolism, obesity, and atherosclerosis. Additionally, for the first time, we present XBP1s-dependent transcriptional reprogramming in metabolic diseases under different conditions, including pathology and physiology. 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Upon endoplasmic reticulum stress, XBP1 is spliced by inositol-requiring enzyme 1 (IRE1), thereby generating functional spliced XBP1 (XBP1s). XBP1s functions by translocating into the nucleus to initiate transcriptional programs that regulate a subset of UPR- and non-UPR-associated genes involved in the pathophysiological processes of various diseases. Recent reports have implicated XBP1 in metabolic diseases. This review summarizes the effects of XBP1-mediated regulation on lipid metabolism, glucose metabolism, obesity, and atherosclerosis. Additionally, for the first time, we present XBP1s-dependent transcriptional reprogramming in metabolic diseases under different conditions, including pathology and physiology. Understanding the function of XBP1 in metabolic diseases may provide a basic knowledge for the development of novel therapeutic targets for ameliorating these diseases.</description><subject>Animals</subject><subject>Cardiovascular Diseases - metabolism</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endoplasmic Reticulum Stress</subject><subject>Endoribonucleases - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Glucose - metabolism</subject><subject>Humans</subject><subject>Lipid Metabolism</subject><subject>Obesity - metabolism</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Regulatory Factor X Transcription Factors</subject><subject>Review</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Unfolded Protein Response</subject><subject>X-Box Binding Protein 1</subject><issn>1044-5498</issn><issn>1557-7430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1r3DAQhkVIaT7aY65Bx1y8kWRpLV8CSUiahUBLaaE3MZbGuwq25EjeDflZ_SP9TbXJB-1phpmHdwYeQk44W3Cm63MXYCEYlwuhlNgjh1ypqqhkyfannklZKFnrA3KU8wNjTAnOPpIDMdWl4OKQhFXYxW6HPYaRxpaOG6Sr7zf8z-_i19U3TgcYN0_wTCE4Og9y4XDA4GZ8TBCyTX4YfQzQ0YRDiusEfe_DmvpAexyhiZ231PmMkDF_Ih9a6DJ-fq3H5OftzY_ru-L-65fV9eV9YUtdjUUpmpo1tpUSGmtdKRuUKEoHUlunta0lSACrKsG1ck60tq1r5-yE1wwtK4_JxUvusG16dHZ6N0FnhuR7SM8mgjf_b4LfmHXcGSk015JPAWevASk-bjGPpvfZYtdBwLjNhi-lWLJlWakJLV5Qm2LOCdv3M5yZ2ZGZHJnZkZkdTfzpv7-9029Syr8vqJFU</recordid><startdate>201501</startdate><enddate>201501</enddate><creator>Wu, Rong</creator><creator>Zhang, Qing-Hai</creator><creator>Lu, Yan-Ju</creator><creator>Ren, Kun</creator><creator>Yi, Guang-Hui</creator><general>Mary Ann Liebert, Inc</general><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>5PM</scope></search><sort><creationdate>201501</creationdate><title>Involvement of the IRE1α-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases</title><author>Wu, Rong ; Zhang, Qing-Hai ; Lu, Yan-Ju ; Ren, Kun ; Yi, Guang-Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-32b90bcf44abccd34be4e23da48cd88c94a4aac572185dd2fcf99ddc4ab90ec03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Cardiovascular Diseases - metabolism</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Endoplasmic Reticulum Stress</topic><topic>Endoribonucleases - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Glucose - metabolism</topic><topic>Humans</topic><topic>Lipid Metabolism</topic><topic>Obesity - metabolism</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Regulatory Factor X Transcription Factors</topic><topic>Review</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Unfolded Protein Response</topic><topic>X-Box Binding Protein 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Rong</creatorcontrib><creatorcontrib>Zhang, Qing-Hai</creatorcontrib><creatorcontrib>Lu, Yan-Ju</creatorcontrib><creatorcontrib>Ren, Kun</creatorcontrib><creatorcontrib>Yi, Guang-Hui</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>DNA and cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Rong</au><au>Zhang, Qing-Hai</au><au>Lu, Yan-Ju</au><au>Ren, Kun</au><au>Yi, Guang-Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of the IRE1α-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases</atitle><jtitle>DNA and cell biology</jtitle><addtitle>DNA Cell Biol</addtitle><date>2015-01</date><risdate>2015</risdate><volume>34</volume><issue>1</issue><spage>6</spage><epage>18</epage><pages>6-18</pages><issn>1044-5498</issn><eissn>1557-7430</eissn><abstract>The X-box binding protein 1 (XBP1) is not only an important component of the unfolded protein response (UPR), but also an important nuclear transcription factor. Upon endoplasmic reticulum stress, XBP1 is spliced by inositol-requiring enzyme 1 (IRE1), thereby generating functional spliced XBP1 (XBP1s). XBP1s functions by translocating into the nucleus to initiate transcriptional programs that regulate a subset of UPR- and non-UPR-associated genes involved in the pathophysiological processes of various diseases. Recent reports have implicated XBP1 in metabolic diseases. This review summarizes the effects of XBP1-mediated regulation on lipid metabolism, glucose metabolism, obesity, and atherosclerosis. Additionally, for the first time, we present XBP1s-dependent transcriptional reprogramming in metabolic diseases under different conditions, including pathology and physiology. Understanding the function of XBP1 in metabolic diseases may provide a basic knowledge for the development of novel therapeutic targets for ameliorating these diseases.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>25216212</pmid><doi>10.1089/dna.2014.2552</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | DNA and cell biology, 2015-01, Vol.34 (1), p.6-18 |
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| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Cardiovascular Diseases - metabolism Diabetes Mellitus, Type 2 - metabolism DNA-Binding Proteins - metabolism Endoplasmic Reticulum Stress Endoribonucleases - metabolism Gene Expression Regulation Glucose - metabolism Humans Lipid Metabolism Obesity - metabolism Protein-Serine-Threonine Kinases - metabolism Regulatory Factor X Transcription Factors Review Transcription Factors - metabolism Transcription, Genetic Unfolded Protein Response X-Box Binding Protein 1 |
| title | Involvement of the IRE1α-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases |
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