Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation
We show that human Cdc14A phosphatase interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in un...
Gespeichert in:
| Veröffentlicht in: | Nature cell biology 2002-04, Vol.4 (4), p.318-322 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 322 |
|---|---|
| container_issue | 4 |
| container_start_page | 318 |
| container_title | Nature cell biology |
| container_volume | 4 |
| creator | Lukas, Jiri Mailand, Niels Lukas, Claudia Kaiser, Brett K Jackson, Peter K Bartek, Jiri |
| description | We show that human Cdc14A phosphatase interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in unperturbed cells selectively contain Cdc14B (ref. 1). Conditional overproduction of Cdc14A, but not its phosphatase-dead or NES-deficient mutants, or Cdc14B, resulted in premature centrosome splitting and formation of supernumerary mitotic spindles. In contrast, downregulation of endogenous Cdc14A by short inhibitory RNA duplexes (siRNA) induced mitotic defects including impaired centrosome separation and failure to undergo productive cytokinesis. Consequently, both overexpression and downregulation of Cdc14A caused aberrant chromosome partitioning into daughter cells. These results indicate that Cdc14A is a physiological regulator of the centrosome duplication cycle, which, when disrupted, can lead to genomic instability in mammalian cells. |
| doi_str_mv | 10.1038/ncb777 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_71592347</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A183287371</galeid><sourcerecordid>A183287371</sourcerecordid><originalsourceid>FETCH-LOGICAL-c521t-cac44c5ad0642d89cfa99af45adb003d1c2583a73acffa18e7b73642f4a0c3da3</originalsourceid><addsrcrecordid>eNqFkluLFDEQhYMo7rrqLxBpFAQfek066Un34zDeFhYEL6-GmqQy00t30psL6L8347TKiGDykKLqOwcOKUIeM3rJKO9eOb2VUt4h50zIVS1Wsr97qFdtLXnfnJEHMd5QyoSg8j45Y6wvdSPOydfXGHCXR0hoqn2ewFUbo5lYV_Pex3kPCSJWZoghzylWGl0KPvoJq4gzBEiDdxU4U-l98NOvya54_hw9JPcsjBEfLe8F-fL2zefN-_r6w7urzfq61m3DUq1BC6FbMHQlGtP12kLfgxWls6WUG6abtuMgOWhrgXUot5IX1AqgmhvgF-TF0XcO_jZjTGoaosZxBIc-RyVZ2zdcyP-CrBOcMsYK-Owv8Mbn4EoI1ZTTcUHbAj0_QjsYUQ3O-hRAHxzVmnW86SSXB6vLf1DlGpwG7R3aofRPBC9PBIVJ-C3tIMeorj59PGWXQLr8Swxo1RyGCcJ3xag6rIY6rkYBny6B8nZC8wdbdqEAT46Ag5QD_gYW_Q8fM7xo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222283405</pqid></control><display><type>article</type><title>Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation</title><source>MEDLINE</source><source>Nature</source><source>Alma/SFX Local Collection</source><creator>Lukas, Jiri ; Mailand, Niels ; Lukas, Claudia ; Kaiser, Brett K ; Jackson, Peter K ; Bartek, Jiri</creator><creatorcontrib>Lukas, Jiri ; Mailand, Niels ; Lukas, Claudia ; Kaiser, Brett K ; Jackson, Peter K ; Bartek, Jiri</creatorcontrib><description>We show that human Cdc14A phosphatase interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in unperturbed cells selectively contain Cdc14B (ref. 1). Conditional overproduction of Cdc14A, but not its phosphatase-dead or NES-deficient mutants, or Cdc14B, resulted in premature centrosome splitting and formation of supernumerary mitotic spindles. In contrast, downregulation of endogenous Cdc14A by short inhibitory RNA duplexes (siRNA) induced mitotic defects including impaired centrosome separation and failure to undergo productive cytokinesis. Consequently, both overexpression and downregulation of Cdc14A caused aberrant chromosome partitioning into daughter cells. These results indicate that Cdc14A is a physiological regulator of the centrosome duplication cycle, which, when disrupted, can lead to genomic instability in mammalian cells.</description><identifier>ISSN: 1465-7392</identifier><identifier>ISSN: 1476-4679</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb777</identifier><identifier>PMID: 11901424</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Amino acids ; Cell cycle ; Cell Cycle Proteins - genetics ; Cell Division ; Cell Line ; Cell Nucleus - metabolism ; Centrosome - metabolism ; Centrosome - ultrastructure ; Centrosomes ; Chromosomes ; Chromosomes - ultrastructure ; Down-Regulation ; Flow Cytometry ; Genetic aspects ; HeLa Cells ; Humans ; Immunoblotting ; Kinetics ; Mammals ; Microscopy, Fluorescence ; Microtubules - ultrastructure ; Mitosis ; Mutation ; Phosphatase ; Phosphatases ; Phosphoric Monoester Hydrolases - metabolism ; Physiological aspects ; Physiology ; Plasmids - metabolism ; Protein Tyrosine Phosphatases ; Proteins ; RNA - ultrastructure ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins ; Schizosaccharomyces - metabolism ; Time Factors ; Transgenes ; Yeast</subject><ispartof>Nature cell biology, 2002-04, Vol.4 (4), p.318-322</ispartof><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-cac44c5ad0642d89cfa99af45adb003d1c2583a73acffa18e7b73642f4a0c3da3</citedby><cites>FETCH-LOGICAL-c521t-cac44c5ad0642d89cfa99af45adb003d1c2583a73acffa18e7b73642f4a0c3da3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2728,27928,27929</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11901424$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lukas, Jiri</creatorcontrib><creatorcontrib>Mailand, Niels</creatorcontrib><creatorcontrib>Lukas, Claudia</creatorcontrib><creatorcontrib>Kaiser, Brett K</creatorcontrib><creatorcontrib>Jackson, Peter K</creatorcontrib><creatorcontrib>Bartek, Jiri</creatorcontrib><title>Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><description>We show that human Cdc14A phosphatase interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in unperturbed cells selectively contain Cdc14B (ref. 1). Conditional overproduction of Cdc14A, but not its phosphatase-dead or NES-deficient mutants, or Cdc14B, resulted in premature centrosome splitting and formation of supernumerary mitotic spindles. In contrast, downregulation of endogenous Cdc14A by short inhibitory RNA duplexes (siRNA) induced mitotic defects including impaired centrosome separation and failure to undergo productive cytokinesis. Consequently, both overexpression and downregulation of Cdc14A caused aberrant chromosome partitioning into daughter cells. These results indicate that Cdc14A is a physiological regulator of the centrosome duplication cycle, which, when disrupted, can lead to genomic instability in mammalian cells.</description><subject>Amino acids</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Division</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>Centrosome - metabolism</subject><subject>Centrosome - ultrastructure</subject><subject>Centrosomes</subject><subject>Chromosomes</subject><subject>Chromosomes - ultrastructure</subject><subject>Down-Regulation</subject><subject>Flow Cytometry</subject><subject>Genetic aspects</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Kinetics</subject><subject>Mammals</subject><subject>Microscopy, Fluorescence</subject><subject>Microtubules - ultrastructure</subject><subject>Mitosis</subject><subject>Mutation</subject><subject>Phosphatase</subject><subject>Phosphatases</subject><subject>Phosphoric Monoester Hydrolases - metabolism</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Plasmids - metabolism</subject><subject>Protein Tyrosine Phosphatases</subject><subject>Proteins</subject><subject>RNA - ultrastructure</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins</subject><subject>Schizosaccharomyces - metabolism</subject><subject>Time Factors</subject><subject>Transgenes</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>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkluLFDEQhYMo7rrqLxBpFAQfek066Un34zDeFhYEL6-GmqQy00t30psL6L8347TKiGDykKLqOwcOKUIeM3rJKO9eOb2VUt4h50zIVS1Wsr97qFdtLXnfnJEHMd5QyoSg8j45Y6wvdSPOydfXGHCXR0hoqn2ewFUbo5lYV_Pex3kPCSJWZoghzylWGl0KPvoJq4gzBEiDdxU4U-l98NOvya54_hw9JPcsjBEfLe8F-fL2zefN-_r6w7urzfq61m3DUq1BC6FbMHQlGtP12kLfgxWls6WUG6abtuMgOWhrgXUot5IX1AqgmhvgF-TF0XcO_jZjTGoaosZxBIc-RyVZ2zdcyP-CrBOcMsYK-Owv8Mbn4EoI1ZTTcUHbAj0_QjsYUQ3O-hRAHxzVmnW86SSXB6vLf1DlGpwG7R3aofRPBC9PBIVJ-C3tIMeorj59PGWXQLr8Swxo1RyGCcJ3xag6rIY6rkYBny6B8nZC8wdbdqEAT46Ag5QD_gYW_Q8fM7xo</recordid><startdate>20020401</startdate><enddate>20020401</enddate><creator>Lukas, Jiri</creator><creator>Mailand, Niels</creator><creator>Lukas, Claudia</creator><creator>Kaiser, Brett K</creator><creator>Jackson, Peter K</creator><creator>Bartek, Jiri</creator><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>20020401</creationdate><title>Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation</title><author>Lukas, Jiri ; Mailand, Niels ; Lukas, Claudia ; Kaiser, Brett K ; Jackson, Peter K ; Bartek, Jiri</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-cac44c5ad0642d89cfa99af45adb003d1c2583a73acffa18e7b73642f4a0c3da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amino acids</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Division</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>Centrosome - metabolism</topic><topic>Centrosome - ultrastructure</topic><topic>Centrosomes</topic><topic>Chromosomes</topic><topic>Chromosomes - ultrastructure</topic><topic>Down-Regulation</topic><topic>Flow Cytometry</topic><topic>Genetic aspects</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Kinetics</topic><topic>Mammals</topic><topic>Microscopy, Fluorescence</topic><topic>Microtubules - ultrastructure</topic><topic>Mitosis</topic><topic>Mutation</topic><topic>Phosphatase</topic><topic>Phosphatases</topic><topic>Phosphoric Monoester Hydrolases - metabolism</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Plasmids - metabolism</topic><topic>Protein Tyrosine Phosphatases</topic><topic>Proteins</topic><topic>RNA - ultrastructure</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Schizosaccharomyces - metabolism</topic><topic>Time Factors</topic><topic>Transgenes</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lukas, Jiri</creatorcontrib><creatorcontrib>Mailand, Niels</creatorcontrib><creatorcontrib>Lukas, Claudia</creatorcontrib><creatorcontrib>Kaiser, Brett K</creatorcontrib><creatorcontrib>Jackson, Peter K</creatorcontrib><creatorcontrib>Bartek, Jiri</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>Lukas, Jiri</au><au>Mailand, Niels</au><au>Lukas, Claudia</au><au>Kaiser, Brett K</au><au>Jackson, Peter K</au><au>Bartek, Jiri</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation</atitle><jtitle>Nature cell biology</jtitle><addtitle>Nat Cell Biol</addtitle><date>2002-04-01</date><risdate>2002</risdate><volume>4</volume><issue>4</issue><spage>318</spage><epage>322</epage><pages>318-322</pages><issn>1465-7392</issn><issn>1476-4679</issn><eissn>1476-4679</eissn><abstract>We show that human Cdc14A phosphatase interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in unperturbed cells selectively contain Cdc14B (ref. 1). Conditional overproduction of Cdc14A, but not its phosphatase-dead or NES-deficient mutants, or Cdc14B, resulted in premature centrosome splitting and formation of supernumerary mitotic spindles. In contrast, downregulation of endogenous Cdc14A by short inhibitory RNA duplexes (siRNA) induced mitotic defects including impaired centrosome separation and failure to undergo productive cytokinesis. Consequently, both overexpression and downregulation of Cdc14A caused aberrant chromosome partitioning into daughter cells. These results indicate that Cdc14A is a physiological regulator of the centrosome duplication cycle, which, when disrupted, can lead to genomic instability in mammalian cells.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>11901424</pmid><doi>10.1038/ncb777</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2002-04, Vol.4 (4), p.318-322 |
| issn | 1465-7392 1476-4679 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71592347 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Amino acids Cell cycle Cell Cycle Proteins - genetics Cell Division Cell Line Cell Nucleus - metabolism Centrosome - metabolism Centrosome - ultrastructure Centrosomes Chromosomes Chromosomes - ultrastructure Down-Regulation Flow Cytometry Genetic aspects HeLa Cells Humans Immunoblotting Kinetics Mammals Microscopy, Fluorescence Microtubules - ultrastructure Mitosis Mutation Phosphatase Phosphatases Phosphoric Monoester Hydrolases - metabolism Physiological aspects Physiology Plasmids - metabolism Protein Tyrosine Phosphatases Proteins RNA - ultrastructure Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins Schizosaccharomyces - metabolism Time Factors Transgenes Yeast |
| title | Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T13%3A12%3A37IST&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=Deregulated%20human%20Cdc14A%20phosphatase%20disrupts%20centrosome%20separation%20and%20chromosome%20segregation&rft.jtitle=Nature%20cell%20biology&rft.au=Lukas,%20Jiri&rft.date=2002-04-01&rft.volume=4&rft.issue=4&rft.spage=318&rft.epage=322&rft.pages=318-322&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/ncb777&rft_dat=%3Cgale_proqu%3EA183287371%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=222283405&rft_id=info:pmid/11901424&rft_galeid=A183287371&rfr_iscdi=true |