The Doc1 subunit is a processivity factor for the anaphase-promoting complex
Ubiquitin-mediated proteolysis of securin and mitotic cyclins is essential for exit from mitosis. The final step in ubiquitination of these and other proteins is catalysed by the anaphase-promoting complex (APC), a multi-subunit ubiquitin-protein ligase (E3). Little is known about the molecular reac...
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| Veröffentlicht in: | Nature cell biology 2002-11, Vol.4 (11), p.880-887 |
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| creator | Carroll, Christopher W. Morgan, David O. |
| description | Ubiquitin-mediated proteolysis of securin and mitotic cyclins is essential for exit from mitosis. The final step in ubiquitination of these and other proteins is catalysed by the anaphase-promoting complex (APC), a multi-subunit ubiquitin-protein ligase (E3). Little is known about the molecular reaction resulting in APC-dependent substrate ubiquitination or the role of individual APC subunits in the reaction. Using a well-defined
in vitro
system, we show that highly purified APC from
Saccharomyces cerevisiae
ubiquitinates a model cyclin substrate in a processive manner. Analysis of mutant APC lacking the Doc1/Apc10 subunit (APC
doc1
Δ
) indicates that Doc1 is required for processivity. The specific molecular defect in APC
doc1Δ
is identified by a large increase in apparent
K
M
for the cyclin substrate relative to the wild-type enzyme. This suggests that Doc1 stimulates processivity by limiting substrate dissociation. Addition of recombinant Doc1 to APC
doc1Δ
fully restores enzyme function. Doc1-related domains are found in mechanistically distinct ubiquitin-ligase enzymes and may generally stimulate ubiquitination by contributing to substrate–enzyme affinity. |
| doi_str_mv | 10.1038/ncb871 |
| format | Article |
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in vitro
system, we show that highly purified APC from
Saccharomyces cerevisiae
ubiquitinates a model cyclin substrate in a processive manner. Analysis of mutant APC lacking the Doc1/Apc10 subunit (APC
doc1
Δ
) indicates that Doc1 is required for processivity. The specific molecular defect in APC
doc1Δ
is identified by a large increase in apparent
K
M
for the cyclin substrate relative to the wild-type enzyme. This suggests that Doc1 stimulates processivity by limiting substrate dissociation. Addition of recombinant Doc1 to APC
doc1Δ
fully restores enzyme function. Doc1-related domains are found in mechanistically distinct ubiquitin-ligase enzymes and may generally stimulate ubiquitination by contributing to substrate–enzyme affinity.</description><identifier>ISSN: 1465-7392</identifier><identifier>ISSN: 1476-4679</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb871</identifier><identifier>PMID: 12402045</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Anaphase ; Anaphase-Promoting Complex-Cyclosome ; Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome ; Biomedical and Life Sciences ; Cancer Research ; Cell Biology ; Cell Cycle ; Cell Cycle Proteins - metabolism ; Cell Cycle Proteins - physiology ; Cellular control mechanisms ; Developmental Biology ; Dose-Response Relationship, Drug ; Enzymes ; Kinetics ; Life Sciences ; Models, Biological ; Mutation ; Physiological aspects ; Protein Binding ; Protein Structure, Tertiary ; Proteins ; Recombinant Proteins - chemistry ; Saccharomyces cerevisiae - physiology ; Saccharomyces cerevisiae Proteins - metabolism ; Saccharomyces cerevisiae Proteins - physiology ; Stem Cells ; Substrate Specificity ; Substrates ; Time Factors ; Ubiquitin ; Ubiquitin - chemistry ; Ubiquitin-Protein Ligase Complexes - metabolism ; Ubiquitin-Protein Ligase Complexes - physiology ; Ubiquitin-Protein Ligases - chemistry ; Ubiquitin-Protein Ligases - physiology ; Yeast</subject><ispartof>Nature cell biology, 2002-11, Vol.4 (11), p.880-887</ispartof><rights>Springer Nature Limited 2002</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Nov 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-c6960ee43c2971c91c5be79d37cfc777b3fd277aba8883715d843fba56225fee3</citedby><cites>FETCH-LOGICAL-c532t-c6960ee43c2971c91c5be79d37cfc777b3fd277aba8883715d843fba56225fee3</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/ncb871$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ncb871$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12402045$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carroll, Christopher W.</creatorcontrib><creatorcontrib>Morgan, David O.</creatorcontrib><title>The Doc1 subunit is a processivity factor for the anaphase-promoting complex</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>Ubiquitin-mediated proteolysis of securin and mitotic cyclins is essential for exit from mitosis. The final step in ubiquitination of these and other proteins is catalysed by the anaphase-promoting complex (APC), a multi-subunit ubiquitin-protein ligase (E3). Little is known about the molecular reaction resulting in APC-dependent substrate ubiquitination or the role of individual APC subunits in the reaction. Using a well-defined
in vitro
system, we show that highly purified APC from
Saccharomyces cerevisiae
ubiquitinates a model cyclin substrate in a processive manner. Analysis of mutant APC lacking the Doc1/Apc10 subunit (APC
doc1
Δ
) indicates that Doc1 is required for processivity. The specific molecular defect in APC
doc1Δ
is identified by a large increase in apparent
K
M
for the cyclin substrate relative to the wild-type enzyme. This suggests that Doc1 stimulates processivity by limiting substrate dissociation. Addition of recombinant Doc1 to APC
doc1Δ
fully restores enzyme function. Doc1-related domains are found in mechanistically distinct ubiquitin-ligase enzymes and may generally stimulate ubiquitination by contributing to substrate–enzyme affinity.</description><subject>Anaphase</subject><subject>Anaphase-Promoting Complex-Cyclosome</subject><subject>Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Cycle</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Cycle Proteins - physiology</subject><subject>Cellular control mechanisms</subject><subject>Developmental Biology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzymes</subject><subject>Kinetics</subject><subject>Life Sciences</subject><subject>Models, Biological</subject><subject>Mutation</subject><subject>Physiological aspects</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Recombinant Proteins - chemistry</subject><subject>Saccharomyces cerevisiae - physiology</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - physiology</subject><subject>Stem Cells</subject><subject>Substrate Specificity</subject><subject>Substrates</subject><subject>Time Factors</subject><subject>Ubiquitin</subject><subject>Ubiquitin - chemistry</subject><subject>Ubiquitin-Protein Ligase Complexes - metabolism</subject><subject>Ubiquitin-Protein Ligase Complexes - physiology</subject><subject>Ubiquitin-Protein Ligases - chemistry</subject><subject>Ubiquitin-Protein Ligases - physiology</subject><subject>Yeast</subject><issn>1465-7392</issn><issn>1476-4679</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqF0u9r1DAYB_AgiptT_wQpDhRfdOZXk_TlmJsODgSdr0OaPrlltMmZpLL99-a4g3FDkBAS0k8e8k2D0FuCzwhm6nOwg5LkGTomXIqWC9k_385F10rW0yP0Kuc7jAnnWL5ER4RyTDHvjtHq5haaL9GSJi_DEnxpfG5Ms0nRQs7-jy8PjTO2xNS42kvVJpjNrcnQVjTH4sO6sXHeTHD_Gr1wZsrwZj-eoF9XlzcX39rV96_XF-er1naMltaKXmAAziztJbE9sd0Ash-ZtM5KKQfmRiqlGYxSiknSjYozN5hOUNo5AHaCPuzq1hP8XiAXPftsYZpMgLhkLakQrGb9LyRKEK5YV-H7J_AuLinUEJrSem2UMlLR6Q6tzQTaBxdLMnZbUZ8TxaiSnMiqzv6hahth9jYGcL6uH2z4dLChmgL3ZW2WnPX1zx-Hdh_IpphzAqc3yc8mPWiC9fYh6N1DqPDdPtAyzDA-sv2fr-DjDuT6KawhPSZ-Uuov_Lq3Tw</recordid><startdate>20021101</startdate><enddate>20021101</enddate><creator>Carroll, Christopher W.</creator><creator>Morgan, David O.</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>AEUYN</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>20021101</creationdate><title>The Doc1 subunit is a processivity factor for the anaphase-promoting complex</title><author>Carroll, Christopher W. ; Morgan, David O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-c6960ee43c2971c91c5be79d37cfc777b3fd277aba8883715d843fba56225fee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Anaphase</topic><topic>Anaphase-Promoting Complex-Cyclosome</topic><topic>Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Cell Cycle</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Cycle Proteins - physiology</topic><topic>Cellular control mechanisms</topic><topic>Developmental Biology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzymes</topic><topic>Kinetics</topic><topic>Life Sciences</topic><topic>Models, Biological</topic><topic>Mutation</topic><topic>Physiological aspects</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Recombinant Proteins - chemistry</topic><topic>Saccharomyces cerevisiae - physiology</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - physiology</topic><topic>Stem Cells</topic><topic>Substrate Specificity</topic><topic>Substrates</topic><topic>Time Factors</topic><topic>Ubiquitin</topic><topic>Ubiquitin - chemistry</topic><topic>Ubiquitin-Protein Ligase Complexes - metabolism</topic><topic>Ubiquitin-Protein Ligase Complexes - physiology</topic><topic>Ubiquitin-Protein Ligases - chemistry</topic><topic>Ubiquitin-Protein Ligases - physiology</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carroll, Christopher W.</creatorcontrib><creatorcontrib>Morgan, David O.</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 One Sustainability</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>Carroll, Christopher W.</au><au>Morgan, David O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Doc1 subunit is a processivity factor for the anaphase-promoting complex</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2002-11-01</date><risdate>2002</risdate><volume>4</volume><issue>11</issue><spage>880</spage><epage>887</epage><pages>880-887</pages><issn>1465-7392</issn><issn>1476-4679</issn><eissn>1476-4679</eissn><abstract>Ubiquitin-mediated proteolysis of securin and mitotic cyclins is essential for exit from mitosis. The final step in ubiquitination of these and other proteins is catalysed by the anaphase-promoting complex (APC), a multi-subunit ubiquitin-protein ligase (E3). Little is known about the molecular reaction resulting in APC-dependent substrate ubiquitination or the role of individual APC subunits in the reaction. Using a well-defined
in vitro
system, we show that highly purified APC from
Saccharomyces cerevisiae
ubiquitinates a model cyclin substrate in a processive manner. Analysis of mutant APC lacking the Doc1/Apc10 subunit (APC
doc1
Δ
) indicates that Doc1 is required for processivity. The specific molecular defect in APC
doc1Δ
is identified by a large increase in apparent
K
M
for the cyclin substrate relative to the wild-type enzyme. This suggests that Doc1 stimulates processivity by limiting substrate dissociation. Addition of recombinant Doc1 to APC
doc1Δ
fully restores enzyme function. Doc1-related domains are found in mechanistically distinct ubiquitin-ligase enzymes and may generally stimulate ubiquitination by contributing to substrate–enzyme affinity.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>12402045</pmid><doi>10.1038/ncb871</doi><tpages>8</tpages></addata></record> |
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| subjects | Anaphase Anaphase-Promoting Complex-Cyclosome Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome Biomedical and Life Sciences Cancer Research Cell Biology Cell Cycle Cell Cycle Proteins - metabolism Cell Cycle Proteins - physiology Cellular control mechanisms Developmental Biology Dose-Response Relationship, Drug Enzymes Kinetics Life Sciences Models, Biological Mutation Physiological aspects Protein Binding Protein Structure, Tertiary Proteins Recombinant Proteins - chemistry Saccharomyces cerevisiae - physiology Saccharomyces cerevisiae Proteins - metabolism Saccharomyces cerevisiae Proteins - physiology Stem Cells Substrate Specificity Substrates Time Factors Ubiquitin Ubiquitin - chemistry Ubiquitin-Protein Ligase Complexes - metabolism Ubiquitin-Protein Ligase Complexes - physiology Ubiquitin-Protein Ligases - chemistry Ubiquitin-Protein Ligases - physiology Yeast |
| title | The Doc1 subunit is a processivity factor for the anaphase-promoting complex |
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