Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation
Division of Endocrinology and Metabolism, Departments of 1 Medicine and 2 Anatomy, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192 Japan Pancreatic duodenal homeobox-1 (Pdx1) is a transcription factor, and its phosphorylation is thought to be essential for activation of insulin gen...
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| Veröffentlicht in: | American journal of physiology: endocrinology and metabolism 2003-04, Vol.284 (4), p.E830-E840 |
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| container_title | American journal of physiology: endocrinology and metabolism |
| container_volume | 284 |
| creator | Kishi, Akio Nakamura, Takaaki Nishio, Yoshihiko Maegawa, Hiroshi Kashiwagi, Atsunori |
| description | Division of Endocrinology and Metabolism, Departments of
1 Medicine and 2 Anatomy, Shiga
University of Medical Science, Seta, Otsu, Shiga 520-2192 Japan
Pancreatic
duodenal homeobox-1 (Pdx1) is a transcription factor, and its
phosphorylation is thought to be essential for activation of insulin
gene expression. This phosphorylation is related to a concomitant shift
in molecular mass from 31 to 46 kDa. However, we found that Pdx1 was
modified by SUMO-1 (small ubiquitin-related modifier 1) in -TC-6 and
COS-7 cells, which were transfected with Pdx1 cDNA. This modification
contributed to the increase in molecular mass of Pdx1 from 31 to
46 kDa. Additionally, sumoylated Pdx1 localized in the nucleus. The
reduction of SUMO-1 protein by use of RNA interference (SUMO-iRNAs)
resulted in a significant decrease in Pdx1 protein in the nucleus. A
34-kDa form of Pdx1 was detected by the cells exposed to SUMO-iRNAs in
the presence of lactacystin, a proteasome inhibitor. Furthermore, the
reduced nuclear sumoylated Pdx1 content was associated with significant lower transcriptional activity of the insulin gene. These findings indicate that SUMO-1 modification is associated with both the localization and stability of Pdx1 as well as its effect on insulin gene activation.
small ubiquitin-related modifier 1; pancreatic duodenal homeobox-1; ribonucleic acid interference |
| doi_str_mv | 10.1152/ajpendo.00390.2002 |
| format | Article |
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1 Medicine and 2 Anatomy, Shiga
University of Medical Science, Seta, Otsu, Shiga 520-2192 Japan
Pancreatic
duodenal homeobox-1 (Pdx1) is a transcription factor, and its
phosphorylation is thought to be essential for activation of insulin
gene expression. This phosphorylation is related to a concomitant shift
in molecular mass from 31 to 46 kDa. However, we found that Pdx1 was
modified by SUMO-1 (small ubiquitin-related modifier 1) in -TC-6 and
COS-7 cells, which were transfected with Pdx1 cDNA. This modification
contributed to the increase in molecular mass of Pdx1 from 31 to
46 kDa. Additionally, sumoylated Pdx1 localized in the nucleus. The
reduction of SUMO-1 protein by use of RNA interference (SUMO-iRNAs)
resulted in a significant decrease in Pdx1 protein in the nucleus. A
34-kDa form of Pdx1 was detected by the cells exposed to SUMO-iRNAs in
the presence of lactacystin, a proteasome inhibitor. Furthermore, the
reduced nuclear sumoylated Pdx1 content was associated with significant lower transcriptional activity of the insulin gene. These findings indicate that SUMO-1 modification is associated with both the localization and stability of Pdx1 as well as its effect on insulin gene activation.
small ubiquitin-related modifier 1; pancreatic duodenal homeobox-1; ribonucleic acid interference</description><identifier>ISSN: 0193-1849</identifier><identifier>EISSN: 1522-1555</identifier><identifier>DOI: 10.1152/ajpendo.00390.2002</identifier><identifier>PMID: 12488243</identifier><language>eng</language><publisher>United States</publisher><subject>Acetylcysteine - analogs & derivatives ; Acetylcysteine - pharmacology ; Animals ; Cell Nucleus - metabolism ; COS Cells ; Cysteine Endopeptidases ; Cysteine Proteinase Inhibitors - pharmacology ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Gene Expression - physiology ; Homeodomain Proteins ; Humans ; Insulin - genetics ; Multienzyme Complexes - antagonists & inhibitors ; Proteasome Endopeptidase Complex ; Protein Processing, Post-Translational - physiology ; RNA, Double-Stranded - pharmacokinetics ; SUMO-1 Protein - genetics ; SUMO-1 Protein - metabolism ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transcription, Genetic - physiology</subject><ispartof>American journal of physiology: endocrinology and metabolism, 2003-04, Vol.284 (4), p.E830-E840</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-da7d0af52637f7d834ef9a628cf99cbf3b226e5449307fe6fe11c99b288453ec3</citedby><cites>FETCH-LOGICAL-c387t-da7d0af52637f7d834ef9a628cf99cbf3b226e5449307fe6fe11c99b288453ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12488243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kishi, Akio</creatorcontrib><creatorcontrib>Nakamura, Takaaki</creatorcontrib><creatorcontrib>Nishio, Yoshihiko</creatorcontrib><creatorcontrib>Maegawa, Hiroshi</creatorcontrib><creatorcontrib>Kashiwagi, Atsunori</creatorcontrib><title>Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation</title><title>American journal of physiology: endocrinology and metabolism</title><addtitle>Am J Physiol Endocrinol Metab</addtitle><description>Division of Endocrinology and Metabolism, Departments of
1 Medicine and 2 Anatomy, Shiga
University of Medical Science, Seta, Otsu, Shiga 520-2192 Japan
Pancreatic
duodenal homeobox-1 (Pdx1) is a transcription factor, and its
phosphorylation is thought to be essential for activation of insulin
gene expression. This phosphorylation is related to a concomitant shift
in molecular mass from 31 to 46 kDa. However, we found that Pdx1 was
modified by SUMO-1 (small ubiquitin-related modifier 1) in -TC-6 and
COS-7 cells, which were transfected with Pdx1 cDNA. This modification
contributed to the increase in molecular mass of Pdx1 from 31 to
46 kDa. Additionally, sumoylated Pdx1 localized in the nucleus. The
reduction of SUMO-1 protein by use of RNA interference (SUMO-iRNAs)
resulted in a significant decrease in Pdx1 protein in the nucleus. A
34-kDa form of Pdx1 was detected by the cells exposed to SUMO-iRNAs in
the presence of lactacystin, a proteasome inhibitor. Furthermore, the
reduced nuclear sumoylated Pdx1 content was associated with significant lower transcriptional activity of the insulin gene. These findings indicate that SUMO-1 modification is associated with both the localization and stability of Pdx1 as well as its effect on insulin gene activation.
small ubiquitin-related modifier 1; pancreatic duodenal homeobox-1; ribonucleic acid interference</description><subject>Acetylcysteine - analogs & derivatives</subject><subject>Acetylcysteine - pharmacology</subject><subject>Animals</subject><subject>Cell Nucleus - metabolism</subject><subject>COS Cells</subject><subject>Cysteine Endopeptidases</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Expression - physiology</subject><subject>Homeodomain Proteins</subject><subject>Humans</subject><subject>Insulin - genetics</subject><subject>Multienzyme Complexes - antagonists & inhibitors</subject><subject>Proteasome Endopeptidase Complex</subject><subject>Protein Processing, Post-Translational - physiology</subject><subject>RNA, Double-Stranded - pharmacokinetics</subject><subject>SUMO-1 Protein - genetics</subject><subject>SUMO-1 Protein - metabolism</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription, Genetic - physiology</subject><issn>0193-1849</issn><issn>1522-1555</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kL1u2zAURomiQe26fYEMBaducvgniRwLI04LBEiBJFMGgiYvbRq0qIpSEufpq9hOM3W6wz3nGw5C55TMKS3Zhdm20Lg0J4QrMmeEsA9oOj5YQcuy_IimhCpeUCnUBH3OeUsIqUvBPqEJZUJKJvgUPdwOu7SPpg-pwcnj3-6Z4pCxyTnZYHpw-Cn0Gxz6jJvBRjAdjsmaGF6OjmkcDk0eYmjwGhrAxvbh8fD7gs68iRm-nu4M3S8v7xY_i-ubq1-LH9eF5bLuC2dqR4wvWcVrXzvJBXhlKiatV8quPF8xVkEphOKk9lB5oNQqtWJSipKD5TP0_bjbdunPALnXu5AtxGgaSEPWNSdKCV6NIDuCtks5d-B124Wd6faaEv2aVJ-S6kNS_Zp0lL6d1ofVDty7cmo4AsUR2IT15il0oNvNPocU03r_b5BJoYW-lJyMvPo_vxxivIPn_k1893TrPP8LlHeaQA</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>Kishi, Akio</creator><creator>Nakamura, Takaaki</creator><creator>Nishio, Yoshihiko</creator><creator>Maegawa, Hiroshi</creator><creator>Kashiwagi, Atsunori</creator><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></search><sort><creationdate>20030401</creationdate><title>Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation</title><author>Kishi, Akio ; Nakamura, Takaaki ; Nishio, Yoshihiko ; Maegawa, Hiroshi ; Kashiwagi, Atsunori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-da7d0af52637f7d834ef9a628cf99cbf3b226e5449307fe6fe11c99b288453ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Acetylcysteine - analogs & derivatives</topic><topic>Acetylcysteine - pharmacology</topic><topic>Animals</topic><topic>Cell Nucleus - metabolism</topic><topic>COS Cells</topic><topic>Cysteine Endopeptidases</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Gene Expression - physiology</topic><topic>Homeodomain Proteins</topic><topic>Humans</topic><topic>Insulin - genetics</topic><topic>Multienzyme Complexes - antagonists & inhibitors</topic><topic>Proteasome Endopeptidase Complex</topic><topic>Protein Processing, Post-Translational - physiology</topic><topic>RNA, Double-Stranded - pharmacokinetics</topic><topic>SUMO-1 Protein - genetics</topic><topic>SUMO-1 Protein - metabolism</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription, Genetic - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kishi, Akio</creatorcontrib><creatorcontrib>Nakamura, Takaaki</creatorcontrib><creatorcontrib>Nishio, Yoshihiko</creatorcontrib><creatorcontrib>Maegawa, Hiroshi</creatorcontrib><creatorcontrib>Kashiwagi, Atsunori</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><jtitle>American journal of physiology: endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kishi, Akio</au><au>Nakamura, Takaaki</au><au>Nishio, Yoshihiko</au><au>Maegawa, Hiroshi</au><au>Kashiwagi, Atsunori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation</atitle><jtitle>American journal of physiology: endocrinology and metabolism</jtitle><addtitle>Am J Physiol Endocrinol Metab</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>284</volume><issue>4</issue><spage>E830</spage><epage>E840</epage><pages>E830-E840</pages><issn>0193-1849</issn><eissn>1522-1555</eissn><abstract>Division of Endocrinology and Metabolism, Departments of
1 Medicine and 2 Anatomy, Shiga
University of Medical Science, Seta, Otsu, Shiga 520-2192 Japan
Pancreatic
duodenal homeobox-1 (Pdx1) is a transcription factor, and its
phosphorylation is thought to be essential for activation of insulin
gene expression. This phosphorylation is related to a concomitant shift
in molecular mass from 31 to 46 kDa. However, we found that Pdx1 was
modified by SUMO-1 (small ubiquitin-related modifier 1) in -TC-6 and
COS-7 cells, which were transfected with Pdx1 cDNA. This modification
contributed to the increase in molecular mass of Pdx1 from 31 to
46 kDa. Additionally, sumoylated Pdx1 localized in the nucleus. The
reduction of SUMO-1 protein by use of RNA interference (SUMO-iRNAs)
resulted in a significant decrease in Pdx1 protein in the nucleus. A
34-kDa form of Pdx1 was detected by the cells exposed to SUMO-iRNAs in
the presence of lactacystin, a proteasome inhibitor. Furthermore, the
reduced nuclear sumoylated Pdx1 content was associated with significant lower transcriptional activity of the insulin gene. These findings indicate that SUMO-1 modification is associated with both the localization and stability of Pdx1 as well as its effect on insulin gene activation.
small ubiquitin-related modifier 1; pancreatic duodenal homeobox-1; ribonucleic acid interference</abstract><cop>United States</cop><pmid>12488243</pmid><doi>10.1152/ajpendo.00390.2002</doi></addata></record> |
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| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
| subjects | Acetylcysteine - analogs & derivatives Acetylcysteine - pharmacology Animals Cell Nucleus - metabolism COS Cells Cysteine Endopeptidases Cysteine Proteinase Inhibitors - pharmacology Fibroblasts - cytology Fibroblasts - metabolism Gene Expression - physiology Homeodomain Proteins Humans Insulin - genetics Multienzyme Complexes - antagonists & inhibitors Proteasome Endopeptidase Complex Protein Processing, Post-Translational - physiology RNA, Double-Stranded - pharmacokinetics SUMO-1 Protein - genetics SUMO-1 Protein - metabolism Trans-Activators - genetics Trans-Activators - metabolism Transcription, Genetic - physiology |
| title | Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation |
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