CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis
Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling ca...
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creator | Huang, Yuejia Wang, Wenwen Yao, Phil Wang, Xiwei Liu, Xing Zhuang, Xiaoxuan Yan, Feng Zhou, Jinhua Du, Jian Ward, Tarsha Zou, Hanfa Zhang, Jiancun Fang, Guowei Ding, Xia Dou, Zhen Yao, Xuebiao |
description | Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation.
Background: CENP-E is a kinetochore-associated kinesin responsible for chromosome congression in mitosis.
Results: CENP-E interacts with SKAP to orchestrate kinetochore-microtubule interaction.
Conclusion: The SKAP-CENP-E interaction links kinetochore structural components to the spindle microtubule attachment in the centromere.
Significance: SKAP cooperates with CENP-E to ensure chromosome stability in cell division. |
doi_str_mv | 10.1074/jbc.M111.277194 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3256856</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925820533851</els_id><sourcerecordid>915040956</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-5e2a310c7adda52d520191aded7b64a92e6d431d79d322c66bbf54b4afe958fc3</originalsourceid><addsrcrecordid>eNp1kU1vGyEQhlHVqnHTnnuruPW0DsPCrrlUsiw3ifJlKa3UG2Jh1ibyLingVPn3IXEatYdwAWmeeRl4CPkMbAqsFUc3nZ1eAMCUty0o8YZMgM3qqpbw6y2ZMMahUlzODsiHlG5YWULBe3LAOQCDWk2IWywvV9WSnvkRkx_p6ZgxGpsT_ePzhl6fzVd0FUPGUsuBXkW7wZSjyUjn1u6eDotNDENIYUB6jeuIa5N9GGnpuPA5JJ8-kne92Sb89Lwfkp_flz8WJ9X51fHpYn5eWSF4riRyUwOzrXHOSO4kZ6DAOHRt1wijODZO1OBa5WrObdN0XS9FJ0yPSs56Wx-Sb_vc2103oLM4lkm3-jb6wcR7HYzX_1dGv9HrcKdrLpuZbErA1-eAGH7vykP14JPF7daMGHZJK5BMMPVEHu1JG0NKEfuXW4DpRzW6qNGPavReTen48u9wL_xfFwVQewDLF915jDpZj6NF5yParF3wr4Y_AB9Zn14</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>915040956</pqid></control><display><type>article</type><title>CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Huang, Yuejia ; Wang, Wenwen ; Yao, Phil ; Wang, Xiwei ; Liu, Xing ; Zhuang, Xiaoxuan ; Yan, Feng ; Zhou, Jinhua ; Du, Jian ; Ward, Tarsha ; Zou, Hanfa ; Zhang, Jiancun ; Fang, Guowei ; Ding, Xia ; Dou, Zhen ; Yao, Xuebiao</creator><creatorcontrib>Huang, Yuejia ; Wang, Wenwen ; Yao, Phil ; Wang, Xiwei ; Liu, Xing ; Zhuang, Xiaoxuan ; Yan, Feng ; Zhou, Jinhua ; Du, Jian ; Ward, Tarsha ; Zou, Hanfa ; Zhang, Jiancun ; Fang, Guowei ; Ding, Xia ; Dou, Zhen ; Yao, Xuebiao</creatorcontrib><description>Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation.
Background: CENP-E is a kinetochore-associated kinesin responsible for chromosome congression in mitosis.
Results: CENP-E interacts with SKAP to orchestrate kinetochore-microtubule interaction.
Conclusion: The SKAP-CENP-E interaction links kinetochore structural components to the spindle microtubule attachment in the centromere.
Significance: SKAP cooperates with CENP-E to ensure chromosome stability in cell division.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M111.277194</identifier><identifier>PMID: 22110139</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Cell Biology ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; CENP-E ; Centromeres ; Checkpoint Control ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomal Proteins, Non-Histone - metabolism ; Chromosome Alignment ; Chromosome Dynamics ; Chromosome Segregation - physiology ; Chromosomes, Human - genetics ; Chromosomes, Human - metabolism ; HeLa Cells ; Humans ; Kinesin - genetics ; Kinesin - metabolism ; Kinetochore ; Kinetochores - metabolism ; Mass Spectrometry (MS) ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; Microtubules - genetics ; Microtubules - metabolism ; Mitosis - physiology ; SKAP ; Spindle Apparatus - genetics ; Spindle Apparatus - metabolism ; Syntelin ; Tubulin</subject><ispartof>The Journal of biological chemistry, 2012-01, Vol.287 (2), p.1500-1509</ispartof><rights>2012 © 2012 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2012 by The American Society for Biochemistry and Molecular Biology, Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-5e2a310c7adda52d520191aded7b64a92e6d431d79d322c66bbf54b4afe958fc3</citedby><cites>FETCH-LOGICAL-c442t-5e2a310c7adda52d520191aded7b64a92e6d431d79d322c66bbf54b4afe958fc3</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/PMC3256856/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256856/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22110139$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Yuejia</creatorcontrib><creatorcontrib>Wang, Wenwen</creatorcontrib><creatorcontrib>Yao, Phil</creatorcontrib><creatorcontrib>Wang, Xiwei</creatorcontrib><creatorcontrib>Liu, Xing</creatorcontrib><creatorcontrib>Zhuang, Xiaoxuan</creatorcontrib><creatorcontrib>Yan, Feng</creatorcontrib><creatorcontrib>Zhou, Jinhua</creatorcontrib><creatorcontrib>Du, Jian</creatorcontrib><creatorcontrib>Ward, Tarsha</creatorcontrib><creatorcontrib>Zou, Hanfa</creatorcontrib><creatorcontrib>Zhang, Jiancun</creatorcontrib><creatorcontrib>Fang, Guowei</creatorcontrib><creatorcontrib>Ding, Xia</creatorcontrib><creatorcontrib>Dou, Zhen</creatorcontrib><creatorcontrib>Yao, Xuebiao</creatorcontrib><title>CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation.
Background: CENP-E is a kinetochore-associated kinesin responsible for chromosome congression in mitosis.
Results: CENP-E interacts with SKAP to orchestrate kinetochore-microtubule interaction.
Conclusion: The SKAP-CENP-E interaction links kinetochore structural components to the spindle microtubule attachment in the centromere.
Significance: SKAP cooperates with CENP-E to ensure chromosome stability in cell division.</description><subject>Cell Biology</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>CENP-E</subject><subject>Centromeres</subject><subject>Checkpoint Control</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>Chromosome Alignment</subject><subject>Chromosome Dynamics</subject><subject>Chromosome Segregation - physiology</subject><subject>Chromosomes, Human - genetics</subject><subject>Chromosomes, Human - metabolism</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinesin - genetics</subject><subject>Kinesin - metabolism</subject><subject>Kinetochore</subject><subject>Kinetochores - metabolism</subject><subject>Mass Spectrometry (MS)</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Microtubules - genetics</subject><subject>Microtubules - metabolism</subject><subject>Mitosis - physiology</subject><subject>SKAP</subject><subject>Spindle Apparatus - genetics</subject><subject>Spindle Apparatus - metabolism</subject><subject>Syntelin</subject><subject>Tubulin</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1vGyEQhlHVqnHTnnuruPW0DsPCrrlUsiw3ifJlKa3UG2Jh1ibyLingVPn3IXEatYdwAWmeeRl4CPkMbAqsFUc3nZ1eAMCUty0o8YZMgM3qqpbw6y2ZMMahUlzODsiHlG5YWULBe3LAOQCDWk2IWywvV9WSnvkRkx_p6ZgxGpsT_ePzhl6fzVd0FUPGUsuBXkW7wZSjyUjn1u6eDotNDENIYUB6jeuIa5N9GGnpuPA5JJ8-kne92Sb89Lwfkp_flz8WJ9X51fHpYn5eWSF4riRyUwOzrXHOSO4kZ6DAOHRt1wijODZO1OBa5WrObdN0XS9FJ0yPSs56Wx-Sb_vc2103oLM4lkm3-jb6wcR7HYzX_1dGv9HrcKdrLpuZbErA1-eAGH7vykP14JPF7daMGHZJK5BMMPVEHu1JG0NKEfuXW4DpRzW6qNGPavReTen48u9wL_xfFwVQewDLF915jDpZj6NF5yParF3wr4Y_AB9Zn14</recordid><startdate>20120106</startdate><enddate>20120106</enddate><creator>Huang, Yuejia</creator><creator>Wang, Wenwen</creator><creator>Yao, Phil</creator><creator>Wang, Xiwei</creator><creator>Liu, Xing</creator><creator>Zhuang, Xiaoxuan</creator><creator>Yan, Feng</creator><creator>Zhou, Jinhua</creator><creator>Du, Jian</creator><creator>Ward, Tarsha</creator><creator>Zou, Hanfa</creator><creator>Zhang, Jiancun</creator><creator>Fang, Guowei</creator><creator>Ding, Xia</creator><creator>Dou, Zhen</creator><creator>Yao, Xuebiao</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120106</creationdate><title>CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis</title><author>Huang, Yuejia ; Wang, Wenwen ; Yao, Phil ; Wang, Xiwei ; Liu, Xing ; Zhuang, Xiaoxuan ; Yan, Feng ; Zhou, Jinhua ; Du, Jian ; Ward, Tarsha ; Zou, Hanfa ; Zhang, Jiancun ; Fang, Guowei ; Ding, Xia ; Dou, Zhen ; Yao, Xuebiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-5e2a310c7adda52d520191aded7b64a92e6d431d79d322c66bbf54b4afe958fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Cell Biology</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>CENP-E</topic><topic>Centromeres</topic><topic>Checkpoint Control</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosomal Proteins, Non-Histone - metabolism</topic><topic>Chromosome Alignment</topic><topic>Chromosome Dynamics</topic><topic>Chromosome Segregation - physiology</topic><topic>Chromosomes, Human - genetics</topic><topic>Chromosomes, Human - metabolism</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinesin - genetics</topic><topic>Kinesin - metabolism</topic><topic>Kinetochore</topic><topic>Kinetochores - metabolism</topic><topic>Mass Spectrometry (MS)</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Microtubules - genetics</topic><topic>Microtubules - metabolism</topic><topic>Mitosis - physiology</topic><topic>SKAP</topic><topic>Spindle Apparatus - genetics</topic><topic>Spindle Apparatus - metabolism</topic><topic>Syntelin</topic><topic>Tubulin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Yuejia</creatorcontrib><creatorcontrib>Wang, Wenwen</creatorcontrib><creatorcontrib>Yao, Phil</creatorcontrib><creatorcontrib>Wang, Xiwei</creatorcontrib><creatorcontrib>Liu, Xing</creatorcontrib><creatorcontrib>Zhuang, Xiaoxuan</creatorcontrib><creatorcontrib>Yan, Feng</creatorcontrib><creatorcontrib>Zhou, Jinhua</creatorcontrib><creatorcontrib>Du, Jian</creatorcontrib><creatorcontrib>Ward, Tarsha</creatorcontrib><creatorcontrib>Zou, Hanfa</creatorcontrib><creatorcontrib>Zhang, Jiancun</creatorcontrib><creatorcontrib>Fang, Guowei</creatorcontrib><creatorcontrib>Ding, Xia</creatorcontrib><creatorcontrib>Dou, Zhen</creatorcontrib><creatorcontrib>Yao, Xuebiao</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Yuejia</au><au>Wang, Wenwen</au><au>Yao, Phil</au><au>Wang, Xiwei</au><au>Liu, Xing</au><au>Zhuang, Xiaoxuan</au><au>Yan, Feng</au><au>Zhou, Jinhua</au><au>Du, Jian</au><au>Ward, Tarsha</au><au>Zou, Hanfa</au><au>Zhang, Jiancun</au><au>Fang, Guowei</au><au>Ding, Xia</au><au>Dou, Zhen</au><au>Yao, Xuebiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2012-01-06</date><risdate>2012</risdate><volume>287</volume><issue>2</issue><spage>1500</spage><epage>1509</epage><pages>1500-1509</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation.
Background: CENP-E is a kinetochore-associated kinesin responsible for chromosome congression in mitosis.
Results: CENP-E interacts with SKAP to orchestrate kinetochore-microtubule interaction.
Conclusion: The SKAP-CENP-E interaction links kinetochore structural components to the spindle microtubule attachment in the centromere.
Significance: SKAP cooperates with CENP-E to ensure chromosome stability in cell division.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22110139</pmid><doi>10.1074/jbc.M111.277194</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Cell Biology Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism CENP-E Centromeres Checkpoint Control Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - metabolism Chromosome Alignment Chromosome Dynamics Chromosome Segregation - physiology Chromosomes, Human - genetics Chromosomes, Human - metabolism HeLa Cells Humans Kinesin - genetics Kinesin - metabolism Kinetochore Kinetochores - metabolism Mass Spectrometry (MS) Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - metabolism Microtubules - genetics Microtubules - metabolism Mitosis - physiology SKAP Spindle Apparatus - genetics Spindle Apparatus - metabolism Syntelin Tubulin |
title | CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis |
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