The Cystatin-Related Epididymal Spermatogenic Protein Inhibits the Serine Protease Prohormone Convertase 2
The cystatin-related epididymal spermatogenic (CRES) protein is related to the family 2 cystatins of the cystatin superfamily of cysteine protease inhibitors. However, CRES lacks sequences important for cysteine protease inhibitory activity and is specifically expressed in reproductive and neuroendo...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2003-03, Vol.144 (3), p.901-908 |
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| creator | Cornwall, Gail A Cameron, Angus Lindberg, Iris Hardy, Daniel M Cormier, Nathaly Hsia, Nelson |
| description | The cystatin-related epididymal spermatogenic (CRES) protein is related to the family 2 cystatins of the cystatin superfamily of cysteine protease inhibitors. However, CRES lacks sequences important for cysteine protease inhibitory activity and is specifically expressed in reproductive and neuroendocrine tissues. Thus, CRES is distinct from cystatins and may perform unique tissue-specific functions. The purpose of the present study was to determine whether CRES functions as a protease inhibitor in in vitro assays. In contrast to mouse recombinant cystatin C, recombinant CRES did not inhibit the cysteine proteases papain and cathepsin B, suggesting that it probably does not function as a typical cystatin. CRES, however, inhibited the serine protease prohormone convertase 2 (PC2), a protease involved in prohormone processing in the neuroendocrine system, whereas cystatin C showed no inhibition. CRES did not inhibit subtilisin, trypsin, or the convertase family members, PC1 and furin, indicating that it selectively inhibits PC2. Kinetic analysis showed that CRES is a competitive inhibitor of PC2 with a Ki of 25 nm. The removal of N-terminal sequences from CRES decreased its affinity for PC2, suggesting that the N terminus may be important for CRES to function as an inhibitor. These studies suggest that CRES is a cross-class inhibitor that may regulate proprotein processing within the reproductive and neuroendocrine systems. |
| doi_str_mv | 10.1210/en.2002-220997 |
| format | Article |
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However, CRES lacks sequences important for cysteine protease inhibitory activity and is specifically expressed in reproductive and neuroendocrine tissues. Thus, CRES is distinct from cystatins and may perform unique tissue-specific functions. The purpose of the present study was to determine whether CRES functions as a protease inhibitor in in vitro assays. In contrast to mouse recombinant cystatin C, recombinant CRES did not inhibit the cysteine proteases papain and cathepsin B, suggesting that it probably does not function as a typical cystatin. CRES, however, inhibited the serine protease prohormone convertase 2 (PC2), a protease involved in prohormone processing in the neuroendocrine system, whereas cystatin C showed no inhibition. CRES did not inhibit subtilisin, trypsin, or the convertase family members, PC1 and furin, indicating that it selectively inhibits PC2. Kinetic analysis showed that CRES is a competitive inhibitor of PC2 with a Ki of 25 nm. The removal of N-terminal sequences from CRES decreased its affinity for PC2, suggesting that the N terminus may be important for CRES to function as an inhibitor. These studies suggest that CRES is a cross-class inhibitor that may regulate proprotein processing within the reproductive and neuroendocrine systems.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2002-220997</identifier><identifier>PMID: 12586766</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Animals ; Binding, Competitive ; Biological and medical sciences ; Cathepsin B ; Cathepsin B - antagonists & inhibitors ; Cell Line ; Cystatin C ; Cystatins - chemistry ; Cystatins - genetics ; Cystatins - pharmacology ; Cysteine ; Cysteine proteinase ; Epididymis - chemistry ; Female ; Fundamental and applied biological sciences. Psychology ; Kinetics ; Male ; Mice ; Neuroendocrine system ; Ovary - chemistry ; Papain ; Papain - antagonists & inhibitors ; Peptide Fragments - pharmacology ; Pituitary Gland, Anterior - chemistry ; Proprotein Convertase 2 ; Proprotein convertases ; Protease ; Protease inhibitors ; Proteinase inhibitors ; Proteins ; Recombinant Fusion Proteins - pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Sequences ; Serine proteinase ; Serine Proteinase Inhibitors - pharmacology ; Structure-Activity Relationship ; Subtilisin ; Subtilisins - antagonists & inhibitors ; Subtilisins - genetics ; Testis - chemistry ; Trypsin</subject><ispartof>Endocrinology (Philadelphia), 2003-03, Vol.144 (3), p.901-908</ispartof><rights>Copyright © 2003 by The Endocrine Society 2003</rights><rights>2003 INIST-CNRS</rights><rights>Copyright © 2003 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-e1886f5d858a6e52fa6d900b9313ad95d70af6b7cebbc54864268bab1c1482af3</citedby><cites>FETCH-LOGICAL-c535t-e1886f5d858a6e52fa6d900b9313ad95d70af6b7cebbc54864268bab1c1482af3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14571678$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12586766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cornwall, Gail A</creatorcontrib><creatorcontrib>Cameron, Angus</creatorcontrib><creatorcontrib>Lindberg, Iris</creatorcontrib><creatorcontrib>Hardy, Daniel M</creatorcontrib><creatorcontrib>Cormier, Nathaly</creatorcontrib><creatorcontrib>Hsia, Nelson</creatorcontrib><title>The Cystatin-Related Epididymal Spermatogenic Protein Inhibits the Serine Protease Prohormone Convertase 2</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>The cystatin-related epididymal spermatogenic (CRES) protein is related to the family 2 cystatins of the cystatin superfamily of cysteine protease inhibitors. However, CRES lacks sequences important for cysteine protease inhibitory activity and is specifically expressed in reproductive and neuroendocrine tissues. Thus, CRES is distinct from cystatins and may perform unique tissue-specific functions. The purpose of the present study was to determine whether CRES functions as a protease inhibitor in in vitro assays. In contrast to mouse recombinant cystatin C, recombinant CRES did not inhibit the cysteine proteases papain and cathepsin B, suggesting that it probably does not function as a typical cystatin. CRES, however, inhibited the serine protease prohormone convertase 2 (PC2), a protease involved in prohormone processing in the neuroendocrine system, whereas cystatin C showed no inhibition. CRES did not inhibit subtilisin, trypsin, or the convertase family members, PC1 and furin, indicating that it selectively inhibits PC2. Kinetic analysis showed that CRES is a competitive inhibitor of PC2 with a Ki of 25 nm. The removal of N-terminal sequences from CRES decreased its affinity for PC2, suggesting that the N terminus may be important for CRES to function as an inhibitor. These studies suggest that CRES is a cross-class inhibitor that may regulate proprotein processing within the reproductive and neuroendocrine systems.</description><subject>Animals</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Cathepsin B</subject><subject>Cathepsin B - antagonists & inhibitors</subject><subject>Cell Line</subject><subject>Cystatin C</subject><subject>Cystatins - chemistry</subject><subject>Cystatins - genetics</subject><subject>Cystatins - pharmacology</subject><subject>Cysteine</subject><subject>Cysteine proteinase</subject><subject>Epididymis - chemistry</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Kinetics</subject><subject>Male</subject><subject>Mice</subject><subject>Neuroendocrine system</subject><subject>Ovary - chemistry</subject><subject>Papain</subject><subject>Papain - antagonists & inhibitors</subject><subject>Peptide Fragments - pharmacology</subject><subject>Pituitary Gland, Anterior - chemistry</subject><subject>Proprotein Convertase 2</subject><subject>Proprotein convertases</subject><subject>Protease</subject><subject>Protease inhibitors</subject><subject>Proteinase inhibitors</subject><subject>Proteins</subject><subject>Recombinant Fusion Proteins - pharmacology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Sequences</subject><subject>Serine proteinase</subject><subject>Serine Proteinase Inhibitors - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Subtilisin</subject><subject>Subtilisins - antagonists & inhibitors</subject><subject>Subtilisins - genetics</subject><subject>Testis - chemistry</subject><subject>Trypsin</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1r3DAQhkVpaDZJrz0WQ2mgB2_1YX34GJa0DQRSmuRsZHnc1WJLriQX9t9XWy9dKOSk0eiZeUfzIvSO4DWhBH8Gt6YY05JSXNfyFVqRuuKlJBK_RiuMCSslpfIcXcS4y9eqqtgbdE4oV0IKsUK7py0Um31MOllX_oBBJ-iK28l2ttuPeigeJwijTv4nOGuK78EnsK64c1vb2hSLlMsfIVgHy5uOf4OtD6PPuY13vyGkQ5ZeobNeDxHeHs9L9Pzl9mnzrbx_-Hq3ubkvDWc8lUCUEj3vFFdaAKe9Fl2NcVszwnRX805i3YtWGmhbwyslKipUq1tiSKWo7tklul76TsH_miGmZrTRwDBoB36OjWSYSSxlBj_8B-78HFyerclamLMaszpT64UywccYoG-mYEcd9g3BzcGDBlxz8KBZPMgF749t53aE7oQfl56Bj0dAR6OHPmhnbDxxFZdESJW5Twvn5-kl0fKfKF9YcJ03Bz-mADGefvTCsH8AEmatHg</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>Cornwall, Gail A</creator><creator>Cameron, Angus</creator><creator>Lindberg, Iris</creator><creator>Hardy, Daniel M</creator><creator>Cormier, Nathaly</creator><creator>Hsia, Nelson</creator><general>Endocrine Society</general><general>Oxford University Press</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20030301</creationdate><title>The Cystatin-Related Epididymal Spermatogenic Protein Inhibits the Serine Protease Prohormone Convertase 2</title><author>Cornwall, Gail A ; Cameron, Angus ; Lindberg, Iris ; Hardy, Daniel M ; Cormier, Nathaly ; Hsia, Nelson</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-e1886f5d858a6e52fa6d900b9313ad95d70af6b7cebbc54864268bab1c1482af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Cathepsin B</topic><topic>Cathepsin B - antagonists & inhibitors</topic><topic>Cell Line</topic><topic>Cystatin C</topic><topic>Cystatins - chemistry</topic><topic>Cystatins - genetics</topic><topic>Cystatins - pharmacology</topic><topic>Cysteine</topic><topic>Cysteine proteinase</topic><topic>Epididymis - chemistry</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Kinetics</topic><topic>Male</topic><topic>Mice</topic><topic>Neuroendocrine system</topic><topic>Ovary - chemistry</topic><topic>Papain</topic><topic>Papain - antagonists & inhibitors</topic><topic>Peptide Fragments - pharmacology</topic><topic>Pituitary Gland, Anterior - chemistry</topic><topic>Proprotein Convertase 2</topic><topic>Proprotein convertases</topic><topic>Protease</topic><topic>Protease inhibitors</topic><topic>Proteinase inhibitors</topic><topic>Proteins</topic><topic>Recombinant Fusion Proteins - pharmacology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Sequences</topic><topic>Serine proteinase</topic><topic>Serine Proteinase Inhibitors - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Subtilisin</topic><topic>Subtilisins - antagonists & inhibitors</topic><topic>Subtilisins - genetics</topic><topic>Testis - chemistry</topic><topic>Trypsin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cornwall, Gail A</creatorcontrib><creatorcontrib>Cameron, Angus</creatorcontrib><creatorcontrib>Lindberg, Iris</creatorcontrib><creatorcontrib>Hardy, Daniel M</creatorcontrib><creatorcontrib>Cormier, Nathaly</creatorcontrib><creatorcontrib>Hsia, Nelson</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology 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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cornwall, Gail A</au><au>Cameron, Angus</au><au>Lindberg, Iris</au><au>Hardy, Daniel M</au><au>Cormier, Nathaly</au><au>Hsia, Nelson</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Cystatin-Related Epididymal Spermatogenic Protein Inhibits the Serine Protease Prohormone Convertase 2</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2003-03-01</date><risdate>2003</risdate><volume>144</volume><issue>3</issue><spage>901</spage><epage>908</epage><pages>901-908</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>The cystatin-related epididymal spermatogenic (CRES) protein is related to the family 2 cystatins of the cystatin superfamily of cysteine protease inhibitors. However, CRES lacks sequences important for cysteine protease inhibitory activity and is specifically expressed in reproductive and neuroendocrine tissues. Thus, CRES is distinct from cystatins and may perform unique tissue-specific functions. The purpose of the present study was to determine whether CRES functions as a protease inhibitor in in vitro assays. In contrast to mouse recombinant cystatin C, recombinant CRES did not inhibit the cysteine proteases papain and cathepsin B, suggesting that it probably does not function as a typical cystatin. CRES, however, inhibited the serine protease prohormone convertase 2 (PC2), a protease involved in prohormone processing in the neuroendocrine system, whereas cystatin C showed no inhibition. CRES did not inhibit subtilisin, trypsin, or the convertase family members, PC1 and furin, indicating that it selectively inhibits PC2. Kinetic analysis showed that CRES is a competitive inhibitor of PC2 with a Ki of 25 nm. The removal of N-terminal sequences from CRES decreased its affinity for PC2, suggesting that the N terminus may be important for CRES to function as an inhibitor. These studies suggest that CRES is a cross-class inhibitor that may regulate proprotein processing within the reproductive and neuroendocrine systems.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>12586766</pmid><doi>10.1210/en.2002-220997</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Binding, Competitive Biological and medical sciences Cathepsin B Cathepsin B - antagonists & inhibitors Cell Line Cystatin C Cystatins - chemistry Cystatins - genetics Cystatins - pharmacology Cysteine Cysteine proteinase Epididymis - chemistry Female Fundamental and applied biological sciences. Psychology Kinetics Male Mice Neuroendocrine system Ovary - chemistry Papain Papain - antagonists & inhibitors Peptide Fragments - pharmacology Pituitary Gland, Anterior - chemistry Proprotein Convertase 2 Proprotein convertases Protease Protease inhibitors Proteinase inhibitors Proteins Recombinant Fusion Proteins - pharmacology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Sequences Serine proteinase Serine Proteinase Inhibitors - pharmacology Structure-Activity Relationship Subtilisin Subtilisins - antagonists & inhibitors Subtilisins - genetics Testis - chemistry Trypsin |
| title | The Cystatin-Related Epididymal Spermatogenic Protein Inhibits the Serine Protease Prohormone Convertase 2 |
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