Securin and B-cyclin/CDK are the only essential targets of the APC
The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis. The complex is composed of at least thirteen core subunits, eight of which are essential, and two activating subunits, Cdc20...
Gespeichert in:
| Veröffentlicht in: | Nature cell biology 2003-12, Vol.5 (12), p.1090-1094 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1094 |
|---|---|
| container_issue | 12 |
| container_start_page | 1090 |
| container_title | Nature cell biology |
| container_volume | 5 |
| creator | Toczyski, David P Thornton, Brian R |
| description | The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis. The complex is composed of at least thirteen core subunits, eight of which are essential, and two activating subunits, Cdc20 (essential) and Cdh1/Hct1 (non-essential). Previously, it was not known which APC targets are sufficient to explain the essential nature of the complex. Here, we show that each of the eight normally essential APC subunits is rendered non-essential ('bypass-suppressed') by the simultaneous removal/inhibition of the APC substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as cells cycle. This suggests that in the absence of B-type cyclin destruction, oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback loops necessary for the bi-stable nature of Clb/CDK activity. These results strongly suggest that securin and B-type cyclin/CDK activity are the only obligatory targets of the APC in Saccharomyces cerevisiae. |
| doi_str_mv | 10.1038/ncb1066 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_71465016</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A632744769</galeid><sourcerecordid>A632744769</sourcerecordid><originalsourceid>FETCH-LOGICAL-c463t-5e642825adaa7603c1516019b521ede2414abf5e437d4240f900e804a80e14ce3</originalsourceid><addsrcrecordid>eNqFkUtP3DAUhS3Uirf6C1pFXdB2Ebh-xE6Ww9AHAgnEY215nJtpUMahtiMx_74eMoBoF8gLWz7fPdfHl5APFA4p8PLI2RkFKTfINhVK5kKq6t3qLItc8YptkZ0Q7gCoEKA2yVYSuJCSb5Pja7SDb11mXJ0d53Zpu9YdTU_OMuMxi78x6123zDAEdLE1XRaNn2MMWd88qpPL6R5535gu4P563yW3P77fTH_l5xc_T6eT89ymbjEvUApWssLUxigJ3NKCSqDVrGAUa2SCCjNrChRc1YIJaCoALEGYEpAKi3yXHIy-977_M2CIetEGi11nHPZD0GoVF6h8E6RlWclSQQI__wPe9YN3KYRmjPEKqmLldjhCc9Ohbl3TR29sWjUuWts7bNp0P5GcKZH-vkoF314VJCbiQ5ybIQR9en31mv0ystb3IXhs9L1vF8YvNQW9mqxeTzaRn9ZvHWYLrF-49SgT8HUEQpLcHP1LmP-9Po6oM3Hw-Oz1pP8FWWWwpw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222390956</pqid></control><display><type>article</type><title>Securin and B-cyclin/CDK are the only essential targets of the APC</title><source>MEDLINE</source><source>SpringerNature Journals</source><source>Nature Journals Online</source><creator>Toczyski, David P ; Thornton, Brian R</creator><creatorcontrib>Toczyski, David P ; Thornton, Brian R</creatorcontrib><description>The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis. The complex is composed of at least thirteen core subunits, eight of which are essential, and two activating subunits, Cdc20 (essential) and Cdh1/Hct1 (non-essential). Previously, it was not known which APC targets are sufficient to explain the essential nature of the complex. Here, we show that each of the eight normally essential APC subunits is rendered non-essential ('bypass-suppressed') by the simultaneous removal/inhibition of the APC substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as cells cycle. This suggests that in the absence of B-type cyclin destruction, oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback loops necessary for the bi-stable nature of Clb/CDK activity. These results strongly suggest that securin and B-type cyclin/CDK activity are the only obligatory targets of the APC in Saccharomyces cerevisiae.</description><identifier>ISSN: 1465-7392</identifier><identifier>ISSN: 1476-4679</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb1066</identifier><identifier>PMID: 14634663</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Anaphase-Promoting Complex-Cyclosome ; Biological research ; Biomedical and Life Sciences ; Cancer Research ; Cell Biology ; Cell Cycle - physiology ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell division ; Cyclin B - metabolism ; Cyclin B1 ; Cyclin-Dependent Kinase Inhibitor Proteins ; Cyclin-Dependent Kinases - metabolism ; Cyclins ; Cytochemistry ; Developmental Biology ; Feedback, Physiological - physiology ; letter ; Life Sciences ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Physiological aspects ; Protein Subunits - metabolism ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - enzymology ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae Proteins - genetics ; Saccharomyces cerevisiae Proteins - metabolism ; Securin ; Stem Cells ; Ubiquitin-proteasome system ; Ubiquitin-Protein Ligase Complexes - genetics ; Ubiquitin-Protein Ligase Complexes - metabolism</subject><ispartof>Nature cell biology, 2003-12, Vol.5 (12), p.1090-1094</ispartof><rights>Springer Nature Limited 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-5e642825adaa7603c1516019b521ede2414abf5e437d4240f900e804a80e14ce3</citedby><cites>FETCH-LOGICAL-c463t-5e642825adaa7603c1516019b521ede2414abf5e437d4240f900e804a80e14ce3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncb1066$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ncb1066$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14634663$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toczyski, David P</creatorcontrib><creatorcontrib>Thornton, Brian R</creatorcontrib><title>Securin and B-cyclin/CDK are the only essential targets of the APC</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis. The complex is composed of at least thirteen core subunits, eight of which are essential, and two activating subunits, Cdc20 (essential) and Cdh1/Hct1 (non-essential). Previously, it was not known which APC targets are sufficient to explain the essential nature of the complex. Here, we show that each of the eight normally essential APC subunits is rendered non-essential ('bypass-suppressed') by the simultaneous removal/inhibition of the APC substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as cells cycle. This suggests that in the absence of B-type cyclin destruction, oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback loops necessary for the bi-stable nature of Clb/CDK activity. These results strongly suggest that securin and B-type cyclin/CDK activity are the only obligatory targets of the APC in Saccharomyces cerevisiae.</description><subject>Anaphase-Promoting Complex-Cyclosome</subject><subject>Biological research</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Cycle - physiology</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell division</subject><subject>Cyclin B - metabolism</subject><subject>Cyclin B1</subject><subject>Cyclin-Dependent Kinase Inhibitor Proteins</subject><subject>Cyclin-Dependent Kinases - metabolism</subject><subject>Cyclins</subject><subject>Cytochemistry</subject><subject>Developmental Biology</subject><subject>Feedback, Physiological - physiology</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Physiological aspects</subject><subject>Protein Subunits - metabolism</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - enzymology</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Securin</subject><subject>Stem Cells</subject><subject>Ubiquitin-proteasome system</subject><subject>Ubiquitin-Protein Ligase Complexes - genetics</subject><subject>Ubiquitin-Protein Ligase Complexes - metabolism</subject><issn>1465-7392</issn><issn>1476-4679</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkUtP3DAUhS3Uirf6C1pFXdB2Ebh-xE6Ww9AHAgnEY215nJtpUMahtiMx_74eMoBoF8gLWz7fPdfHl5APFA4p8PLI2RkFKTfINhVK5kKq6t3qLItc8YptkZ0Q7gCoEKA2yVYSuJCSb5Pja7SDb11mXJ0d53Zpu9YdTU_OMuMxi78x6123zDAEdLE1XRaNn2MMWd88qpPL6R5535gu4P563yW3P77fTH_l5xc_T6eT89ymbjEvUApWssLUxigJ3NKCSqDVrGAUa2SCCjNrChRc1YIJaCoALEGYEpAKi3yXHIy-977_M2CIetEGi11nHPZD0GoVF6h8E6RlWclSQQI__wPe9YN3KYRmjPEKqmLldjhCc9Ohbl3TR29sWjUuWts7bNp0P5GcKZH-vkoF314VJCbiQ5ybIQR9en31mv0ystb3IXhs9L1vF8YvNQW9mqxeTzaRn9ZvHWYLrF-49SgT8HUEQpLcHP1LmP-9Po6oM3Hw-Oz1pP8FWWWwpw</recordid><startdate>20031201</startdate><enddate>20031201</enddate><creator>Toczyski, David P</creator><creator>Thornton, Brian R</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20031201</creationdate><title>Securin and B-cyclin/CDK are the only essential targets of the APC</title><author>Toczyski, David P ; Thornton, Brian R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-5e642825adaa7603c1516019b521ede2414abf5e437d4240f900e804a80e14ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Anaphase-Promoting Complex-Cyclosome</topic><topic>Biological research</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Cell Cycle - physiology</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell division</topic><topic>Cyclin B - metabolism</topic><topic>Cyclin B1</topic><topic>Cyclin-Dependent Kinase Inhibitor Proteins</topic><topic>Cyclin-Dependent Kinases - metabolism</topic><topic>Cyclins</topic><topic>Cytochemistry</topic><topic>Developmental Biology</topic><topic>Feedback, Physiological - physiology</topic><topic>letter</topic><topic>Life Sciences</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Physiological aspects</topic><topic>Protein Subunits - metabolism</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - enzymology</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>Securin</topic><topic>Stem Cells</topic><topic>Ubiquitin-proteasome system</topic><topic>Ubiquitin-Protein Ligase Complexes - genetics</topic><topic>Ubiquitin-Protein Ligase Complexes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toczyski, David P</creatorcontrib><creatorcontrib>Thornton, Brian R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toczyski, David P</au><au>Thornton, Brian R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Securin and B-cyclin/CDK are the only essential targets of the APC</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2003-12-01</date><risdate>2003</risdate><volume>5</volume><issue>12</issue><spage>1090</spage><epage>1094</epage><pages>1090-1094</pages><issn>1465-7392</issn><issn>1476-4679</issn><eissn>1476-4679</eissn><abstract>The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis. The complex is composed of at least thirteen core subunits, eight of which are essential, and two activating subunits, Cdc20 (essential) and Cdh1/Hct1 (non-essential). Previously, it was not known which APC targets are sufficient to explain the essential nature of the complex. Here, we show that each of the eight normally essential APC subunits is rendered non-essential ('bypass-suppressed') by the simultaneous removal/inhibition of the APC substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as cells cycle. This suggests that in the absence of B-type cyclin destruction, oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback loops necessary for the bi-stable nature of Clb/CDK activity. These results strongly suggest that securin and B-type cyclin/CDK activity are the only obligatory targets of the APC in Saccharomyces cerevisiae.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>14634663</pmid><doi>10.1038/ncb1066</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2003-12, Vol.5 (12), p.1090-1094 |
| issn | 1465-7392 1476-4679 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71465016 |
| source | MEDLINE; SpringerNature Journals; Nature Journals Online |
| subjects | Anaphase-Promoting Complex-Cyclosome Biological research Biomedical and Life Sciences Cancer Research Cell Biology Cell Cycle - physiology Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell division Cyclin B - metabolism Cyclin B1 Cyclin-Dependent Kinase Inhibitor Proteins Cyclin-Dependent Kinases - metabolism Cyclins Cytochemistry Developmental Biology Feedback, Physiological - physiology letter Life Sciences Nuclear Proteins - genetics Nuclear Proteins - metabolism Physiological aspects Protein Subunits - metabolism Saccharomyces cerevisiae Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Securin Stem Cells Ubiquitin-proteasome system Ubiquitin-Protein Ligase Complexes - genetics Ubiquitin-Protein Ligase Complexes - metabolism |
| title | Securin and B-cyclin/CDK are the only essential targets of the APC |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T22%3A40%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Securin%20and%20B-cyclin/CDK%20are%20the%20only%20essential%20targets%20of%20the%20APC&rft.jtitle=Nature%20cell%20biology&rft.au=Toczyski,%20David%20P&rft.date=2003-12-01&rft.volume=5&rft.issue=12&rft.spage=1090&rft.epage=1094&rft.pages=1090-1094&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/ncb1066&rft_dat=%3Cgale_proqu%3EA632744769%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222390956&rft_id=info:pmid/14634663&rft_galeid=A632744769&rfr_iscdi=true |