KCTD10 is involved in the cardiovascular system and Notch signaling during early embryonic development
As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase δ, participates in DNA repair, DNA replication and cell-cycle control. In order to fu...
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| creator | Ren, Kaiqun Yuan, Jing Yang, Manjun Gao, Xiang Ding, Xiaofeng Zhou, Jianlin Hu, Xingwang Cao, Jianguo Deng, Xiyun Xiang, Shuanglin Zhang, Jian |
| description | As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase δ, participates in DNA repair, DNA replication and cell-cycle control. In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10(+/-) mice were viable and fertile, while the homozygous KCTD10(-/-) mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway. |
| doi_str_mv | 10.1371/journal.pone.0112275 |
| format | Article |
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In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10(+/-) mice were viable and fertile, while the homozygous KCTD10(-/-) mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0112275</identifier><identifier>PMID: 25401743</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Angiogenesis ; Animals ; Biology and Life Sciences ; Cardiovascular system ; Cardiovascular System - embryology ; Cardiovascular System - metabolism ; Cell cycle ; Cell Line ; Cullin Proteins - metabolism ; Defects ; Deoxyribonucleic acid ; Developmental biology ; DNA ; DNA biosynthesis ; DNA repair ; DNA replication ; Education ; Embryogenesis ; Embryonic development ; Embryonic Development - genetics ; Embryonic growth stage ; Embryos ; Gene Deletion ; Gene Expression Regulation, Developmental - drug effects ; Gene Order ; Genes, Lethal ; Genetic Loci ; Heart ; Heart Defects, Congenital - genetics ; Heart Defects, Congenital - pathology ; Humans ; Immunoprecipitation ; Laboratories ; Life sciences ; Ligands ; Mammals ; Medicine and Health Sciences ; Mice ; Mice, Knockout ; Mutation ; Neovascularization, Physiologic - genetics ; Notch protein ; Notch1 protein ; Physiological aspects ; Placenta ; Potassium ; Potassium Channels, Voltage-Gated - genetics ; Potassium Channels, Voltage-Gated - metabolism ; Proliferating cell nuclear antigen ; Protein Binding ; Proteins ; Proteolysis ; Receptors, Notch - metabolism ; Research and Analysis Methods ; Signal Transduction ; Signaling ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - pharmacology ; Western blotting</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e112275-e112275</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Ren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Ren et al 2014 Ren et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-5710ee020de3562b713bc01c43b35a204bffb2cfdf2a6098088b53cbd2434b483</citedby><cites>FETCH-LOGICAL-c758t-5710ee020de3562b713bc01c43b35a204bffb2cfdf2a6098088b53cbd2434b483</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/PMC4234411/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234411/$$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/25401743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Dettman, Robert W.</contributor><creatorcontrib>Ren, Kaiqun</creatorcontrib><creatorcontrib>Yuan, Jing</creatorcontrib><creatorcontrib>Yang, Manjun</creatorcontrib><creatorcontrib>Gao, Xiang</creatorcontrib><creatorcontrib>Ding, Xiaofeng</creatorcontrib><creatorcontrib>Zhou, Jianlin</creatorcontrib><creatorcontrib>Hu, Xingwang</creatorcontrib><creatorcontrib>Cao, Jianguo</creatorcontrib><creatorcontrib>Deng, Xiyun</creatorcontrib><creatorcontrib>Xiang, Shuanglin</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><title>KCTD10 is involved in the cardiovascular system and Notch signaling during early embryonic development</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase δ, participates in DNA repair, DNA replication and cell-cycle control. In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10(+/-) mice were viable and fertile, while the homozygous KCTD10(-/-) mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway.</description><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Cardiovascular system</subject><subject>Cardiovascular System - embryology</subject><subject>Cardiovascular System - metabolism</subject><subject>Cell cycle</subject><subject>Cell Line</subject><subject>Cullin Proteins - metabolism</subject><subject>Defects</subject><subject>Deoxyribonucleic acid</subject><subject>Developmental biology</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA repair</subject><subject>DNA replication</subject><subject>Education</subject><subject>Embryogenesis</subject><subject>Embryonic development</subject><subject>Embryonic Development - genetics</subject><subject>Embryonic growth stage</subject><subject>Embryos</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Gene Order</subject><subject>Genes, Lethal</subject><subject>Genetic Loci</subject><subject>Heart</subject><subject>Heart Defects, Congenital - genetics</subject><subject>Heart Defects, Congenital - pathology</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Laboratories</subject><subject>Life sciences</subject><subject>Ligands</subject><subject>Mammals</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mutation</subject><subject>Neovascularization, Physiologic - genetics</subject><subject>Notch protein</subject><subject>Notch1 protein</subject><subject>Physiological aspects</subject><subject>Placenta</subject><subject>Potassium</subject><subject>Potassium Channels, Voltage-Gated - genetics</subject><subject>Potassium Channels, Voltage-Gated - metabolism</subject><subject>Proliferating cell nuclear antigen</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>Receptors, Notch - metabolism</subject><subject>Research and Analysis Methods</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - pharmacology</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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><sourceid>DOA</sourceid><recordid>eNqNk21v0zAQxyMEYmPwDRBEQkLwosWPSfoGaep4qJiYBIO3lmNfUldOXOykot9-zppNDdoLZFk-2b_7n-_sS5KXGM0xzfGHjet9K-1861qYI4wJyfmj5BQvKJllBNHHR_ZJ8iyEDUKcFln2NDkhnCGcM3qaVN-W1xcYpSakpt05uwMdjbRbQ6qk18btZFC9lT4N-9BBk8pWp99dp9ZpMHWMb9o61b0fFpDe7lNoSr93rVGphh1Yt22g7Z4nTyppA7wY17Pk1-dP18uvs8urL6vl-eVM5bzoZjzHCAARpIHyjJQ5pqVCWDFaUi4JYmVVlURVuiIyQ4sCFUXJqSo1YZSVrKBnyeuD7ta6IMYSBYEzwnmeZQWJxOpAaCc3YutNI_1eOGnE7YbztZC-M8qCqHjGJeWEUr5gHPKSaio5FLmWBeYoj1ofx2h92YBWMVEv7UR0etKatajdTjBCGcM4CrwbBbz700PoRGOCAmtlC66_vXcWJ86GWG_-QR_ObqRqGRMwbeViXDWIinOGC0ZYjoYqzR-g4tDQGBX_U2Xi_sTh_cQhMh387WrZhyBWP3_8P3v1e8q-PWLXIG23Ds72nXFtmILsACrvQvBQ3RcZIzG0w101xNAOYmyH6Pbq-IHune7-P70B2ToEOA</recordid><startdate>20141117</startdate><enddate>20141117</enddate><creator>Ren, Kaiqun</creator><creator>Yuan, Jing</creator><creator>Yang, Manjun</creator><creator>Gao, Xiang</creator><creator>Ding, Xiaofeng</creator><creator>Zhou, Jianlin</creator><creator>Hu, Xingwang</creator><creator>Cao, Jianguo</creator><creator>Deng, Xiyun</creator><creator>Xiang, Shuanglin</creator><creator>Zhang, Jian</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141117</creationdate><title>KCTD10 is involved in the cardiovascular system and Notch signaling during early embryonic development</title><author>Ren, Kaiqun ; Yuan, Jing ; Yang, Manjun ; Gao, Xiang ; Ding, Xiaofeng ; Zhou, Jianlin ; Hu, Xingwang ; Cao, Jianguo ; Deng, Xiyun ; Xiang, Shuanglin ; Zhang, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-5710ee020de3562b713bc01c43b35a204bffb2cfdf2a6098088b53cbd2434b483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Cardiovascular system</topic><topic>Cardiovascular System - embryology</topic><topic>Cardiovascular System - metabolism</topic><topic>Cell cycle</topic><topic>Cell Line</topic><topic>Cullin Proteins - metabolism</topic><topic>Defects</topic><topic>Deoxyribonucleic acid</topic><topic>Developmental biology</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA repair</topic><topic>DNA replication</topic><topic>Education</topic><topic>Embryogenesis</topic><topic>Embryonic development</topic><topic>Embryonic Development - genetics</topic><topic>Embryonic growth stage</topic><topic>Embryos</topic><topic>Gene Deletion</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Gene Order</topic><topic>Genes, Lethal</topic><topic>Genetic Loci</topic><topic>Heart</topic><topic>Heart Defects, Congenital - genetics</topic><topic>Heart Defects, Congenital - pathology</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Laboratories</topic><topic>Life sciences</topic><topic>Ligands</topic><topic>Mammals</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mutation</topic><topic>Neovascularization, Physiologic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ren, Kaiqun</au><au>Yuan, Jing</au><au>Yang, Manjun</au><au>Gao, Xiang</au><au>Ding, Xiaofeng</au><au>Zhou, Jianlin</au><au>Hu, Xingwang</au><au>Cao, Jianguo</au><au>Deng, Xiyun</au><au>Xiang, Shuanglin</au><au>Zhang, Jian</au><au>Dettman, Robert W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>KCTD10 is involved in the cardiovascular system and Notch signaling during early embryonic development</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-17</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e112275</spage><epage>e112275</epage><pages>e112275-e112275</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase δ, participates in DNA repair, DNA replication and cell-cycle control. In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10(+/-) mice were viable and fertile, while the homozygous KCTD10(-/-) mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25401743</pmid><doi>10.1371/journal.pone.0112275</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1625576682 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Angiogenesis Animals Biology and Life Sciences Cardiovascular system Cardiovascular System - embryology Cardiovascular System - metabolism Cell cycle Cell Line Cullin Proteins - metabolism Defects Deoxyribonucleic acid Developmental biology DNA DNA biosynthesis DNA repair DNA replication Education Embryogenesis Embryonic development Embryonic Development - genetics Embryonic growth stage Embryos Gene Deletion Gene Expression Regulation, Developmental - drug effects Gene Order Genes, Lethal Genetic Loci Heart Heart Defects, Congenital - genetics Heart Defects, Congenital - pathology Humans Immunoprecipitation Laboratories Life sciences Ligands Mammals Medicine and Health Sciences Mice Mice, Knockout Mutation Neovascularization, Physiologic - genetics Notch protein Notch1 protein Physiological aspects Placenta Potassium Potassium Channels, Voltage-Gated - genetics Potassium Channels, Voltage-Gated - metabolism Proliferating cell nuclear antigen Protein Binding Proteins Proteolysis Receptors, Notch - metabolism Research and Analysis Methods Signal Transduction Signaling Vascular endothelial growth factor Vascular Endothelial Growth Factor A - pharmacology Western blotting |
| title | KCTD10 is involved in the cardiovascular system and Notch signaling during early embryonic development |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T12%3A22%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=KCTD10%20is%20involved%20in%20the%20cardiovascular%20system%20and%20Notch%20signaling%20during%20early%20embryonic%20development&rft.jtitle=PloS%20one&rft.au=Ren,%20Kaiqun&rft.date=2014-11-17&rft.volume=9&rft.issue=11&rft.spage=e112275&rft.epage=e112275&rft.pages=e112275-e112275&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0112275&rft_dat=%3Cgale_plos_%3EA418424708%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1625576682&rft_id=info:pmid/25401743&rft_galeid=A418424708&rft_doaj_id=oai_doaj_org_article_f565a352335945e7b3d3a5e87da81507&rfr_iscdi=true |