E1 ubiquitin-activating enzyme UBA-1 plays multiple roles throughout C. elegans development
Poly-ubiquitination of target proteins typically marks them for destruction via the proteasome and provides an essential mechanism for the dynamic control of protein levels. The E1 ubiquitin-activating enzyme lies at the apex of the ubiquitination cascade, and its activity is necessary for all subse...
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| creator | Kulkarni, Madhura Smith, Harold E |
| description | Poly-ubiquitination of target proteins typically marks them for destruction via the proteasome and provides an essential mechanism for the dynamic control of protein levels. The E1 ubiquitin-activating enzyme lies at the apex of the ubiquitination cascade, and its activity is necessary for all subsequent steps in the reaction. We have isolated a temperature-sensitive mutation in the Caenorhabditis elegans uba-1 gene, which encodes the sole E1 enzyme in this organism. Manipulation of UBA-1 activity at different developmental stages reveals a variety of functions for ubiquitination, including novel roles in sperm fertility, control of body size, and sex-specific development. Levels of ubiquitin conjugates are substantially reduced in the mutant, consistent with reduced E1 activity. The uba-1 mutation causes delays in meiotic progression in the early embryo, a process that is known to be regulated by ubiquitin-mediated proteolysis. The uba-1 mutation also demonstrates synthetic lethal interactions with alleles of the anaphase-promoting complex, an E3 ubiquitin ligase. The uba-1 mutation provides a sensitized genetic background for identifying new in vivo functions for downstream components of the ubiquitin enzyme cascade, and it is one of the first conditional mutations reported for the essential E1 enzyme in a metazoan animal model. |
| doi_str_mv | 10.1371/journal.pgen.1000131 |
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The E1 ubiquitin-activating enzyme lies at the apex of the ubiquitination cascade, and its activity is necessary for all subsequent steps in the reaction. We have isolated a temperature-sensitive mutation in the Caenorhabditis elegans uba-1 gene, which encodes the sole E1 enzyme in this organism. Manipulation of UBA-1 activity at different developmental stages reveals a variety of functions for ubiquitination, including novel roles in sperm fertility, control of body size, and sex-specific development. Levels of ubiquitin conjugates are substantially reduced in the mutant, consistent with reduced E1 activity. The uba-1 mutation causes delays in meiotic progression in the early embryo, a process that is known to be regulated by ubiquitin-mediated proteolysis. The uba-1 mutation also demonstrates synthetic lethal interactions with alleles of the anaphase-promoting complex, an E3 ubiquitin ligase. The uba-1 mutation provides a sensitized genetic background for identifying new in vivo functions for downstream components of the ubiquitin enzyme cascade, and it is one of the first conditional mutations reported for the essential E1 enzyme in a metazoan animal model.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1000131</identifier><identifier>PMID: 18636104</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alleles ; Anaphase-Promoting Complex-Cyclosome ; Animals ; Caenorhabditis elegans ; Caenorhabditis elegans - embryology ; Caenorhabditis elegans - enzymology ; Caenorhabditis elegans - growth & development ; Caenorhabditis elegans Proteins - metabolism ; Developmental Biology ; Developmental Biology/Germ Cells ; Embryo, Nonmammalian ; Enzymes ; Fluorescent Dyes - metabolism ; Genes ; Genes, Helminth ; Genetic Complementation Test ; Genetics ; Genetics and Genomics/Gene Function ; Heterozygote ; Homozygote ; Hydrolysis ; Indoles - metabolism ; Male ; Meiosis ; Metazoa ; Mutation ; Nematoda ; Proteins ; Spermatozoa - abnormalities ; Spermatozoa - cytology ; Spermatozoa - metabolism ; Ubiquitin-Activating Enzymes - genetics ; Ubiquitin-Activating Enzymes - metabolism ; Ubiquitin-Protein Ligase Complexes - genetics ; Ubiquitin-Protein Ligase Complexes - metabolism ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism ; Ubiquitination ; Ubiquitins - genetics ; Ubiquitins - metabolism</subject><ispartof>PLoS genetics, 2008-07, Vol.4 (7), p.e1000131-e1000131</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>Kulkarni et al. 2008</rights><rights>2008 Kulkarni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Kulkarni M, Smith HE (2008) E1 Ubiquitin-Activating Enzyme UBA-1 Plays Multiple Roles throughout C. elegans Development. PLoS Genet 4(7): e1000131. doi:10.1371/journal.pgen.1000131</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c817t-be89278c7d8980b868617a73096fbb557d78bc5d8e4f95e573b5e9ccdc407f573</citedby><cites>FETCH-LOGICAL-c817t-be89278c7d8980b868617a73096fbb557d78bc5d8e4f95e573b5e9ccdc407f573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2443343/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2443343/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18636104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mullins, Mary</contributor><creatorcontrib>Kulkarni, Madhura</creatorcontrib><creatorcontrib>Smith, Harold E</creatorcontrib><title>E1 ubiquitin-activating enzyme UBA-1 plays multiple roles throughout C. elegans development</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Poly-ubiquitination of target proteins typically marks them for destruction via the proteasome and provides an essential mechanism for the dynamic control of protein levels. The E1 ubiquitin-activating enzyme lies at the apex of the ubiquitination cascade, and its activity is necessary for all subsequent steps in the reaction. We have isolated a temperature-sensitive mutation in the Caenorhabditis elegans uba-1 gene, which encodes the sole E1 enzyme in this organism. Manipulation of UBA-1 activity at different developmental stages reveals a variety of functions for ubiquitination, including novel roles in sperm fertility, control of body size, and sex-specific development. Levels of ubiquitin conjugates are substantially reduced in the mutant, consistent with reduced E1 activity. The uba-1 mutation causes delays in meiotic progression in the early embryo, a process that is known to be regulated by ubiquitin-mediated proteolysis. The uba-1 mutation also demonstrates synthetic lethal interactions with alleles of the anaphase-promoting complex, an E3 ubiquitin ligase. The uba-1 mutation provides a sensitized genetic background for identifying new in vivo functions for downstream components of the ubiquitin enzyme cascade, and it is one of the first conditional mutations reported for the essential E1 enzyme in a metazoan animal model.</description><subject>Alleles</subject><subject>Anaphase-Promoting Complex-Cyclosome</subject><subject>Animals</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - embryology</subject><subject>Caenorhabditis elegans - enzymology</subject><subject>Caenorhabditis elegans - growth & development</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Developmental Biology</subject><subject>Developmental Biology/Germ Cells</subject><subject>Embryo, Nonmammalian</subject><subject>Enzymes</subject><subject>Fluorescent Dyes - metabolism</subject><subject>Genes</subject><subject>Genes, Helminth</subject><subject>Genetic Complementation Test</subject><subject>Genetics</subject><subject>Genetics and Genomics/Gene Function</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Hydrolysis</subject><subject>Indoles - metabolism</subject><subject>Male</subject><subject>Meiosis</subject><subject>Metazoa</subject><subject>Mutation</subject><subject>Nematoda</subject><subject>Proteins</subject><subject>Spermatozoa - abnormalities</subject><subject>Spermatozoa - cytology</subject><subject>Spermatozoa - metabolism</subject><subject>Ubiquitin-Activating Enzymes - genetics</subject><subject>Ubiquitin-Activating Enzymes - metabolism</subject><subject>Ubiquitin-Protein Ligase Complexes - genetics</subject><subject>Ubiquitin-Protein Ligase Complexes - metabolism</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Ubiquitination</subject><subject>Ubiquitins - genetics</subject><subject>Ubiquitins - metabolism</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVk9-LEzEQxxdRvLP6H4guCAc-tCabzSZ5EWo5tXB4oJ4vPoRsdnabkt3sbbLF-teb2qotiD9IIJnJZ74hM5kkeYzRDBOGX6zdOHTKzvoGuhlGCGGC7yTnmFIyZTnK7x7tz5IH3q8RIpQLdj85w7wgBUb5efL5EqdjaW5HE0w3VTqYjYq7JoXu67aF9ObVfIrT3qqtT9vRBtNbSAdnwadhNbixWbkxpItZChYa1fm0gg1Y17fQhYfJvVpZD48O6yS5eX35cfF2enX9ZrmYX001xyxMS-AiY1yziguOSl7wAjPFCBJFXZaUsorxUtOKQ14LCpSRkoLQutI5YnU0J8nTvW5vnZeHvHgZ80FoniHB_0hkghQ7YrknKqfWsh9Mq4atdMrI7w43NFINwWgLkkNNacEIYwLnumJC1CUWOit3Zl1UUevl4baxbKHSMRWDsieipyedWcnGbWSW54TEOUkuDgKDux3BB9kar8Fa1YEbvSwEyQjO8r-CGUaxzHSn-GwPNiq-wHS1ixfrHSznGYpiWAgRqdlvqDgqaI12HdQm-k8Cnp8ERCbAl9Co0Xu5_PD-P9h3_85efzplL47YFSgbVt7ZMRjX-VMw34N6cN4PUP-sCEZy11I_PobctZQ8tFQMe3JczV9Bhx4i3wCkWxku</recordid><startdate>200807</startdate><enddate>200807</enddate><creator>Kulkarni, Madhura</creator><creator>Smith, Harold E</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>200807</creationdate><title>E1 ubiquitin-activating enzyme UBA-1 plays multiple roles throughout C. elegans development</title><author>Kulkarni, Madhura ; Smith, Harold E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c817t-be89278c7d8980b868617a73096fbb557d78bc5d8e4f95e573b5e9ccdc407f573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Alleles</topic><topic>Anaphase-Promoting Complex-Cyclosome</topic><topic>Animals</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - embryology</topic><topic>Caenorhabditis elegans - enzymology</topic><topic>Caenorhabditis elegans - growth & development</topic><topic>Caenorhabditis elegans Proteins - metabolism</topic><topic>Developmental Biology</topic><topic>Developmental Biology/Germ Cells</topic><topic>Embryo, Nonmammalian</topic><topic>Enzymes</topic><topic>Fluorescent Dyes - metabolism</topic><topic>Genes</topic><topic>Genes, Helminth</topic><topic>Genetic Complementation Test</topic><topic>Genetics</topic><topic>Genetics and Genomics/Gene Function</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Hydrolysis</topic><topic>Indoles - metabolism</topic><topic>Male</topic><topic>Meiosis</topic><topic>Metazoa</topic><topic>Mutation</topic><topic>Nematoda</topic><topic>Proteins</topic><topic>Spermatozoa - abnormalities</topic><topic>Spermatozoa - cytology</topic><topic>Spermatozoa - metabolism</topic><topic>Ubiquitin-Activating Enzymes - genetics</topic><topic>Ubiquitin-Activating Enzymes - metabolism</topic><topic>Ubiquitin-Protein Ligase Complexes - genetics</topic><topic>Ubiquitin-Protein Ligase Complexes - metabolism</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><topic>Ubiquitination</topic><topic>Ubiquitins - genetics</topic><topic>Ubiquitins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kulkarni, Madhura</creatorcontrib><creatorcontrib>Smith, Harold E</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: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kulkarni, Madhura</au><au>Smith, Harold E</au><au>Mullins, Mary</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>E1 ubiquitin-activating enzyme UBA-1 plays multiple roles throughout C. elegans development</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2008-07</date><risdate>2008</risdate><volume>4</volume><issue>7</issue><spage>e1000131</spage><epage>e1000131</epage><pages>e1000131-e1000131</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Poly-ubiquitination of target proteins typically marks them for destruction via the proteasome and provides an essential mechanism for the dynamic control of protein levels. The E1 ubiquitin-activating enzyme lies at the apex of the ubiquitination cascade, and its activity is necessary for all subsequent steps in the reaction. We have isolated a temperature-sensitive mutation in the Caenorhabditis elegans uba-1 gene, which encodes the sole E1 enzyme in this organism. Manipulation of UBA-1 activity at different developmental stages reveals a variety of functions for ubiquitination, including novel roles in sperm fertility, control of body size, and sex-specific development. Levels of ubiquitin conjugates are substantially reduced in the mutant, consistent with reduced E1 activity. The uba-1 mutation causes delays in meiotic progression in the early embryo, a process that is known to be regulated by ubiquitin-mediated proteolysis. The uba-1 mutation also demonstrates synthetic lethal interactions with alleles of the anaphase-promoting complex, an E3 ubiquitin ligase. The uba-1 mutation provides a sensitized genetic background for identifying new in vivo functions for downstream components of the ubiquitin enzyme cascade, and it is one of the first conditional mutations reported for the essential E1 enzyme in a metazoan animal model.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18636104</pmid><doi>10.1371/journal.pgen.1000131</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Alleles Anaphase-Promoting Complex-Cyclosome Animals Caenorhabditis elegans Caenorhabditis elegans - embryology Caenorhabditis elegans - enzymology Caenorhabditis elegans - growth & development Caenorhabditis elegans Proteins - metabolism Developmental Biology Developmental Biology/Germ Cells Embryo, Nonmammalian Enzymes Fluorescent Dyes - metabolism Genes Genes, Helminth Genetic Complementation Test Genetics Genetics and Genomics/Gene Function Heterozygote Homozygote Hydrolysis Indoles - metabolism Male Meiosis Metazoa Mutation Nematoda Proteins Spermatozoa - abnormalities Spermatozoa - cytology Spermatozoa - metabolism Ubiquitin-Activating Enzymes - genetics Ubiquitin-Activating Enzymes - metabolism Ubiquitin-Protein Ligase Complexes - genetics Ubiquitin-Protein Ligase Complexes - metabolism Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitination Ubiquitins - genetics Ubiquitins - metabolism |
| title | E1 ubiquitin-activating enzyme UBA-1 plays multiple roles throughout C. elegans development |
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