The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast
Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological t...
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| Veröffentlicht in: | Genes & development 1999-03, Vol.13 (5), p.532-544 |
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| creator | Biggins, S Severin, F F Bhalla, N Sassoon, I Hyman, A A Murray, A W |
| description | Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are regulated during the cell cycle. This pattern of localization and regulation is similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2 protein. Because aurora2 has been implicated in oncogenesis, defects in kinetochore function may contribute to genetic instability in human tumors. |
| doi_str_mv | 10.1101/gad.13.5.532 |
| format | Article |
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We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are regulated during the cell cycle. This pattern of localization and regulation is similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2 protein. Because aurora2 has been implicated in oncogenesis, defects in kinetochore function may contribute to genetic instability in human tumors.</description><identifier>ISSN: 0890-9369</identifier><identifier>DOI: 10.1101/gad.13.5.532</identifier><identifier>PMID: 10072382</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Aurora Kinases ; Cell Cycle ; Chromatids ; DNA-Binding Proteins - metabolism ; Fungal Proteins - metabolism ; Intracellular Signaling Peptides and Proteins ; Kinetochores - metabolism ; Microtubules - metabolism ; Mutagenesis ; Phosphorylation ; Protein Kinases - genetics ; Protein Kinases - metabolism ; Protein-Serine-Threonine Kinases ; Research Paper ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins ; Saccharomycetales - enzymology ; Spindle Apparatus - metabolism</subject><ispartof>Genes & development, 1999-03, Vol.13 (5), p.532-544</ispartof><rights>Copyright © 1999, Cold Spring Harbor Laboratory Press 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC316509/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC316509/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10072382$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Biggins, S</creatorcontrib><creatorcontrib>Severin, F F</creatorcontrib><creatorcontrib>Bhalla, N</creatorcontrib><creatorcontrib>Sassoon, I</creatorcontrib><creatorcontrib>Hyman, A A</creatorcontrib><creatorcontrib>Murray, A W</creatorcontrib><title>The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are regulated during the cell cycle. This pattern of localization and regulation is similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2 protein. Because aurora2 has been implicated in oncogenesis, defects in kinetochore function may contribute to genetic instability in human tumors.</description><subject>Aurora Kinases</subject><subject>Cell Cycle</subject><subject>Chromatids</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Fungal Proteins - metabolism</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Kinetochores - metabolism</subject><subject>Microtubules - metabolism</subject><subject>Mutagenesis</subject><subject>Phosphorylation</subject><subject>Protein Kinases - genetics</subject><subject>Protein Kinases - metabolism</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Research Paper</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae Proteins</subject><subject>Saccharomycetales - enzymology</subject><subject>Spindle Apparatus - metabolism</subject><issn>0890-9369</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkDtPwzAURj2AaClszMgTW4MdNw8PDKjiUakSS5mDHzepIbGD7SD135NCQTBd6X7n3E-6CF1QklBK6HUjdEJZkiUZS4_QlJSczDnL-QSdhvBKCMlJnp-gCSWkSFmZTtHLZgtYORvAf4DGvXcRjMVvxooAeNW3FHtohlZECLgzaswHObSApbHa2AZHt4chOrV1fmRGWQ76K9qBCPEMHdeiDXB-mDP0fH-3WT7O108Pq-Xtet6n6SLOlZKal7pmQtCMCMVFkWlZK1oLKQllIi84Ba2Bas4WXI0bKPdSmRNOdcFm6Ob7bj_IDrQCG71oq96bTvhd5YSp_ifWbKvGfVSM5hnho3918L17HyDEqjNBQdsKC24IFS3SlLB0MYKXf4t-G35-yj4BI7V7Eg</recordid><startdate>19990301</startdate><enddate>19990301</enddate><creator>Biggins, S</creator><creator>Severin, F F</creator><creator>Bhalla, N</creator><creator>Sassoon, I</creator><creator>Hyman, A A</creator><creator>Murray, A W</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>19990301</creationdate><title>The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast</title><author>Biggins, S ; Severin, F F ; Bhalla, N ; Sassoon, I ; Hyman, A A ; Murray, A W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p224t-ccbd98df3aa150ac9a75dbfc1fabb013a6791edde1d9349c13ae8ccbd86091d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Aurora Kinases</topic><topic>Cell Cycle</topic><topic>Chromatids</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Fungal Proteins - metabolism</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Kinetochores - metabolism</topic><topic>Microtubules - metabolism</topic><topic>Mutagenesis</topic><topic>Phosphorylation</topic><topic>Protein Kinases - genetics</topic><topic>Protein Kinases - metabolism</topic><topic>Protein-Serine-Threonine Kinases</topic><topic>Research Paper</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Saccharomycetales - enzymology</topic><topic>Spindle Apparatus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Biggins, S</creatorcontrib><creatorcontrib>Severin, F F</creatorcontrib><creatorcontrib>Bhalla, N</creatorcontrib><creatorcontrib>Sassoon, I</creatorcontrib><creatorcontrib>Hyman, A A</creatorcontrib><creatorcontrib>Murray, A W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Biggins, S</au><au>Severin, F F</au><au>Bhalla, N</au><au>Sassoon, I</au><au>Hyman, A A</au><au>Murray, A W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>1999-03-01</date><risdate>1999</risdate><volume>13</volume><issue>5</issue><spage>532</spage><epage>544</epage><pages>532-544</pages><issn>0890-9369</issn><abstract>Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are regulated during the cell cycle. This pattern of localization and regulation is similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2 protein. Because aurora2 has been implicated in oncogenesis, defects in kinetochore function may contribute to genetic instability in human tumors.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>10072382</pmid><doi>10.1101/gad.13.5.532</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Genes & development, 1999-03, Vol.13 (5), p.532-544 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Aurora Kinases Cell Cycle Chromatids DNA-Binding Proteins - metabolism Fungal Proteins - metabolism Intracellular Signaling Peptides and Proteins Kinetochores - metabolism Microtubules - metabolism Mutagenesis Phosphorylation Protein Kinases - genetics Protein Kinases - metabolism Protein-Serine-Threonine Kinases Research Paper Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Saccharomycetales - enzymology Spindle Apparatus - metabolism |
| title | The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast |
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