Identification and Analysis of the Gene Encoding Human PC2, a Prohormone Convertase Expressed in Neuroendocrine Tissues
In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-06, Vol.89 (11), p.4977-4981 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Ohagi, Shinya LaMendola, Joseph LeBeau, Michelle M. Espinosa, Rafael Takeda, Jun Smeekens, Steven P. Chan, Shu Jin Steiner, Donald F. |
| description | In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans >130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in βTC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity. |
| doi_str_mv | 10.1073/pnas.89.11.4977 |
| format | Article |
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PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans >130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in βTC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.11.4977</identifier><identifier>PMID: 1594602</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Base Sequence ; Biological and medical sciences ; Chromosomes ; Chromosomes, Human, Pair 20 ; Cloning, Molecular ; Complementary DNA ; Deoxyribonucleic acid ; DNA ; Endocrine system ; Exons ; Fundamental and applied biological sciences. Psychology ; Genes ; Genes. Genome ; Genetics ; Hep G2 cells ; Hormones ; Humans ; Introns ; Islets of Langerhans ; Messenger RNA ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Plasmids ; Promoter regions ; Promoter Regions, Genetic ; Proprotein Convertase 2 ; Protein Precursors - metabolism ; Restriction Mapping ; Sequence Alignment ; Serine Endopeptidases - genetics</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-06, Vol.89 (11), p.4977-4981</ispartof><rights>Copyright 1992 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Jun 1, 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-1b3c496948ff1100ff7ef4978cb864708249c79abf6ce955ac799ad2c89c8d823</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/89/11.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2359570$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2359570$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5371097$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1594602$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohagi, Shinya</creatorcontrib><creatorcontrib>LaMendola, Joseph</creatorcontrib><creatorcontrib>LeBeau, Michelle M.</creatorcontrib><creatorcontrib>Espinosa, Rafael</creatorcontrib><creatorcontrib>Takeda, Jun</creatorcontrib><creatorcontrib>Smeekens, Steven P.</creatorcontrib><creatorcontrib>Chan, Shu Jin</creatorcontrib><creatorcontrib>Steiner, Donald F.</creatorcontrib><title>Identification and Analysis of the Gene Encoding Human PC2, a Prohormone Convertase Expressed in Neuroendocrine Tissues</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans >130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in βTC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity.</description><subject>Amino Acid Sequence</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 20</subject><subject>Cloning, Molecular</subject><subject>Complementary DNA</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Endocrine system</subject><subject>Exons</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Genes. Genome</subject><subject>Genetics</subject><subject>Hep G2 cells</subject><subject>Hormones</subject><subject>Humans</subject><subject>Introns</subject><subject>Islets of Langerhans</subject><subject>Messenger RNA</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Plasmids</subject><subject>Promoter regions</subject><subject>Promoter Regions, Genetic</subject><subject>Proprotein Convertase 2</subject><subject>Protein Precursors - metabolism</subject><subject>Restriction Mapping</subject><subject>Sequence Alignment</subject><subject>Serine Endopeptidases - genetics</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ksFvFCEYxSfGpq7Vsxc1xJh6cbbAMAMkXppNbZs02kM9E5aBLpsZ2PLN1Pa_l8muq_XgiZD3-x4PHkXxhuA5wbw62QQNcyHnhMyZ5PxZMSNYkrJhEj8vZhhTXgpG2YviJcAaYyxrgQ-LQ1JL1mA6K35etjYM3nmjBx8D0qFFp0F3j-ABRYeGlUXnNlh0FkxsfbhFF2OvA7pe0M9Io-sUVzH1MQOLGO5tGjRk9mGTLIBtkQ_omx1TtKGNJvmM3XiA0cKr4sDpDuzr3XpU_Ph6drO4KK--n18uTq9KUws2lGRZGSYbyYRzhGDsHLcuX1SYpWgYx4IyabjUS9cYK-ta543ULTVCGtEKWh0VX7a-m3HZ29bkyybdqU3yvU6PKmqvnirBr9RtvFdMUkLy-PFuPMW7HHtQvQdju04HG0dQnOZwguIMfvgHXMcx5YcERTGhleRscjvZQiZFgGTdPgfBaqpTTXUqIRUhaqozT7z7O_4ffttf1j_udA1Gdy7pYDzssbri-TtMNu932OT_W31yzqf_AsqNXTfYhyGTb7fkGoaY9iitallzXP0CV4PLdQ</recordid><startdate>19920601</startdate><enddate>19920601</enddate><creator>Ohagi, Shinya</creator><creator>LaMendola, Joseph</creator><creator>LeBeau, Michelle M.</creator><creator>Espinosa, Rafael</creator><creator>Takeda, Jun</creator><creator>Smeekens, Steven P.</creator><creator>Chan, Shu Jin</creator><creator>Steiner, Donald F.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><scope>IQODW</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19920601</creationdate><title>Identification and Analysis of the Gene Encoding Human PC2, a Prohormone Convertase Expressed in Neuroendocrine Tissues</title><author>Ohagi, Shinya ; LaMendola, Joseph ; LeBeau, Michelle M. ; Espinosa, Rafael ; Takeda, Jun ; Smeekens, Steven P. ; Chan, Shu Jin ; Steiner, Donald F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-1b3c496948ff1100ff7ef4978cb864708249c79abf6ce955ac799ad2c89c8d823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Amino Acid Sequence</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 20</topic><topic>Cloning, Molecular</topic><topic>Complementary DNA</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Endocrine system</topic><topic>Exons</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes</topic><topic>Genes. Genome</topic><topic>Genetics</topic><topic>Hep G2 cells</topic><topic>Hormones</topic><topic>Humans</topic><topic>Introns</topic><topic>Islets of Langerhans</topic><topic>Messenger RNA</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>Plasmids</topic><topic>Promoter regions</topic><topic>Promoter Regions, Genetic</topic><topic>Proprotein Convertase 2</topic><topic>Protein Precursors - metabolism</topic><topic>Restriction Mapping</topic><topic>Sequence Alignment</topic><topic>Serine Endopeptidases - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohagi, Shinya</creatorcontrib><creatorcontrib>LaMendola, Joseph</creatorcontrib><creatorcontrib>LeBeau, Michelle M.</creatorcontrib><creatorcontrib>Espinosa, Rafael</creatorcontrib><creatorcontrib>Takeda, Jun</creatorcontrib><creatorcontrib>Smeekens, Steven P.</creatorcontrib><creatorcontrib>Chan, Shu Jin</creatorcontrib><creatorcontrib>Steiner, Donald F.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</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>Ohagi, Shinya</au><au>LaMendola, Joseph</au><au>LeBeau, Michelle M.</au><au>Espinosa, Rafael</au><au>Takeda, Jun</au><au>Smeekens, Steven P.</au><au>Chan, Shu Jin</au><au>Steiner, Donald F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and Analysis of the Gene Encoding Human PC2, a Prohormone Convertase Expressed in Neuroendocrine Tissues</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1992-06-01</date><risdate>1992</risdate><volume>89</volume><issue>11</issue><spage>4977</spage><epage>4981</epage><pages>4977-4981</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans >130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in βTC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1594602</pmid><doi>10.1073/pnas.89.11.4977</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | PubMed (Medline); Jstor Complete Legacy; MEDLINE; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence Base Sequence Biological and medical sciences Chromosomes Chromosomes, Human, Pair 20 Cloning, Molecular Complementary DNA Deoxyribonucleic acid DNA Endocrine system Exons Fundamental and applied biological sciences. Psychology Genes Genes. Genome Genetics Hep G2 cells Hormones Humans Introns Islets of Langerhans Messenger RNA Molecular and cellular biology Molecular genetics Molecular Sequence Data Plasmids Promoter regions Promoter Regions, Genetic Proprotein Convertase 2 Protein Precursors - metabolism Restriction Mapping Sequence Alignment Serine Endopeptidases - genetics |
| title | Identification and Analysis of the Gene Encoding Human PC2, a Prohormone Convertase Expressed in Neuroendocrine Tissues |
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