Proper CycE–Cdk2 activity in endocycling tissues requires regulation of the cyclin-dependent kinase inhibitor Dacapo by dE2F1b in Drosophila
Abstract Polyploidy is an integral part of development and is associated with cellular stress, aging, and pathological conditions. The endocycle, comprised of successive rounds of G and S phases without mitosis, is widely employed to produce polyploid cells in plants and animals. In Drosophila, main...
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| Veröffentlicht in: | Genetics (Austin) 2021-03, Vol.217 (1), p.1-15 |
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| creator | Kim, Minhee Delos Santos, Keemo Moon, Nam-Sung |
| description | Abstract
Polyploidy is an integral part of development and is associated with cellular stress, aging, and pathological conditions. The endocycle, comprised of successive rounds of G and S phases without mitosis, is widely employed to produce polyploid cells in plants and animals. In Drosophila, maintenance of the endocycle is dependent on E2F-governed oscillations of Cyclin E (CycE)–Cdk2 activity, which is known to be largely regulated at the level of transcription. In this study, we report an additional level of E2F-dependent control of CycE–Cdk2 activity during the endocycle. Genetic experiments revealed that an alternative isoform of Drosophila de2f1, dE2F1b, regulates the expression of the p27CIP/KIP-like Cdk inhibitor Dacapo (Dap). We provide evidence showing that dE2F1b-dependent Dap expression in endocycling tissues is necessary for setting proper CycE–Cdk2 activity. Furthermore, we demonstrate that dE2F1b is required for proliferating cell nuclear antigen expression that establishes a negative feedback loop in S phase. Overall, our study reveals previously unappreciated E2F-dependent regulatory networks that are critical for the periodic transition between G and S phases during the endocycle. |
| doi_str_mv | 10.1093/genetics/iyaa029 |
| format | Article |
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Polyploidy is an integral part of development and is associated with cellular stress, aging, and pathological conditions. The endocycle, comprised of successive rounds of G and S phases without mitosis, is widely employed to produce polyploid cells in plants and animals. In Drosophila, maintenance of the endocycle is dependent on E2F-governed oscillations of Cyclin E (CycE)–Cdk2 activity, which is known to be largely regulated at the level of transcription. In this study, we report an additional level of E2F-dependent control of CycE–Cdk2 activity during the endocycle. Genetic experiments revealed that an alternative isoform of Drosophila de2f1, dE2F1b, regulates the expression of the p27CIP/KIP-like Cdk inhibitor Dacapo (Dap). We provide evidence showing that dE2F1b-dependent Dap expression in endocycling tissues is necessary for setting proper CycE–Cdk2 activity. Furthermore, we demonstrate that dE2F1b is required for proliferating cell nuclear antigen expression that establishes a negative feedback loop in S phase. Overall, our study reveals previously unappreciated E2F-dependent regulatory networks that are critical for the periodic transition between G and S phases during the endocycle.</description><identifier>ISSN: 1943-2631</identifier><identifier>ISSN: 0016-6731</identifier><identifier>EISSN: 1943-2631</identifier><identifier>DOI: 10.1093/genetics/iyaa029</identifier><identifier>PMID: 33683365</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Aging ; Animals ; Antigens ; Cell Cycle ; Control theory ; Cyclin E ; Cyclin E - genetics ; Cyclin E - metabolism ; Cyclin-dependent kinase 2 ; Cyclin-Dependent Kinase 2 - genetics ; Cyclin-Dependent Kinase 2 - metabolism ; Cyclin-dependent kinases ; Drosophila ; Drosophila melanogaster ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; E2F protein ; Enzyme inhibitors ; Feedback loops ; Feedback, Physiological ; Fruit flies ; Genetics ; Insects ; Investigation ; Kinases ; Kip protein ; Mitosis ; Negative feedback ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Oscillations ; Plant cells ; Polyploidy ; Proliferating cell nuclear antigen ; Proliferating Cell Nuclear Antigen - genetics ; Proliferating Cell Nuclear Antigen - metabolism ; S phase ; Transcription ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Genetics (Austin), 2021-03, Vol.217 (1), p.1-15</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com 2021</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-9e69640cbc0263c9e4b34589d750bf1e9c5a914f45f47d2fcd9c7540b790d48c3</citedby><cites>FETCH-LOGICAL-c460t-9e69640cbc0263c9e4b34589d750bf1e9c5a914f45f47d2fcd9c7540b790d48c3</cites><orcidid>0000-0002-8135-645X ; 0000-0002-0455-927X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33683365$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Duronio, R</contributor><creatorcontrib>Kim, Minhee</creatorcontrib><creatorcontrib>Delos Santos, Keemo</creatorcontrib><creatorcontrib>Moon, Nam-Sung</creatorcontrib><title>Proper CycE–Cdk2 activity in endocycling tissues requires regulation of the cyclin-dependent kinase inhibitor Dacapo by dE2F1b in Drosophila</title><title>Genetics (Austin)</title><addtitle>Genetics</addtitle><description>Abstract
Polyploidy is an integral part of development and is associated with cellular stress, aging, and pathological conditions. The endocycle, comprised of successive rounds of G and S phases without mitosis, is widely employed to produce polyploid cells in plants and animals. In Drosophila, maintenance of the endocycle is dependent on E2F-governed oscillations of Cyclin E (CycE)–Cdk2 activity, which is known to be largely regulated at the level of transcription. In this study, we report an additional level of E2F-dependent control of CycE–Cdk2 activity during the endocycle. Genetic experiments revealed that an alternative isoform of Drosophila de2f1, dE2F1b, regulates the expression of the p27CIP/KIP-like Cdk inhibitor Dacapo (Dap). We provide evidence showing that dE2F1b-dependent Dap expression in endocycling tissues is necessary for setting proper CycE–Cdk2 activity. Furthermore, we demonstrate that dE2F1b is required for proliferating cell nuclear antigen expression that establishes a negative feedback loop in S phase. Overall, our study reveals previously unappreciated E2F-dependent regulatory networks that are critical for the periodic transition between G and S phases during the endocycle.</description><subject>Aging</subject><subject>Animals</subject><subject>Antigens</subject><subject>Cell Cycle</subject><subject>Control theory</subject><subject>Cyclin E</subject><subject>Cyclin E - genetics</subject><subject>Cyclin E - metabolism</subject><subject>Cyclin-dependent kinase 2</subject><subject>Cyclin-Dependent Kinase 2 - genetics</subject><subject>Cyclin-Dependent Kinase 2 - metabolism</subject><subject>Cyclin-dependent kinases</subject><subject>Drosophila</subject><subject>Drosophila melanogaster</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>E2F protein</subject><subject>Enzyme inhibitors</subject><subject>Feedback loops</subject><subject>Feedback, Physiological</subject><subject>Fruit flies</subject><subject>Genetics</subject><subject>Insects</subject><subject>Investigation</subject><subject>Kinases</subject><subject>Kip protein</subject><subject>Mitosis</subject><subject>Negative feedback</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Oscillations</subject><subject>Plant cells</subject><subject>Polyploidy</subject><subject>Proliferating cell nuclear antigen</subject><subject>Proliferating Cell Nuclear Antigen - genetics</subject><subject>Proliferating Cell Nuclear Antigen - metabolism</subject><subject>S phase</subject><subject>Transcription</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>1943-2631</issn><issn>0016-6731</issn><issn>1943-2631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxi0EoqVw54QscUFCoePE-eMLUrXd0kqVygHOluNMdt1m7dR2KuXGE3DhDXkSvOy2Kr1wsDySf_N5vvkIecvgEwNRHK_QYjQ6HJtZKcjFM3LIBC-yvCrY80f1AXkVwjUAVKJsXpKDoqiadMpD8vOrdyN6upj18vePX4vuJqdKR3Nn4kyNpWg7p2c9GLui0YQwYaAebyfj_xaraVDROEtdT-Ma6Q7NOhxTI9pIb4xVAZPS2rQmOk9PlVajo-1Mu2V-xtrtJ6feBTeuzaBekxe9GgK-2d9H5PvZ8tviPLu8-nKxOLnMNK8gZgIrUXHQrYZkTwvkbcHLRnR1CW3PUOhSCcZ7Xva87vJed0LXJYe2FtDxRhdH5PNOd5zaDXY6jerVIEdvNsrP0ikj_32xZi1X7k42wMuqEUngw17Au9u0lCg3JmgcBmXRTUHmXAiAmtUsoe-foNdu8jbZ21K8AJHzPFGwo3RaRvDYPwzDQG7Dlvdhy33YqeXdYxMPDffpJuDjDnDT-H-5PyLUu5o</recordid><startdate>20210303</startdate><enddate>20210303</enddate><creator>Kim, Minhee</creator><creator>Delos Santos, Keemo</creator><creator>Moon, Nam-Sung</creator><general>Oxford University Press</general><general>Genetics Society of America</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>4T-</scope><scope>4U-</scope><scope>7QP</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8135-645X</orcidid><orcidid>https://orcid.org/0000-0002-0455-927X</orcidid></search><sort><creationdate>20210303</creationdate><title>Proper CycE–Cdk2 activity in endocycling tissues requires regulation of the cyclin-dependent kinase inhibitor Dacapo by dE2F1b in Drosophila</title><author>Kim, Minhee ; Delos Santos, Keemo ; Moon, Nam-Sung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-9e69640cbc0263c9e4b34589d750bf1e9c5a914f45f47d2fcd9c7540b790d48c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Antigens</topic><topic>Cell Cycle</topic><topic>Control theory</topic><topic>Cyclin E</topic><topic>Cyclin E - genetics</topic><topic>Cyclin E - metabolism</topic><topic>Cyclin-dependent kinase 2</topic><topic>Cyclin-Dependent Kinase 2 - genetics</topic><topic>Cyclin-Dependent Kinase 2 - metabolism</topic><topic>Cyclin-dependent kinases</topic><topic>Drosophila</topic><topic>Drosophila melanogaster</topic><topic>Drosophila Proteins - genetics</topic><topic>Drosophila Proteins - metabolism</topic><topic>E2F protein</topic><topic>Enzyme inhibitors</topic><topic>Feedback loops</topic><topic>Feedback, Physiological</topic><topic>Fruit flies</topic><topic>Genetics</topic><topic>Insects</topic><topic>Investigation</topic><topic>Kinases</topic><topic>Kip protein</topic><topic>Mitosis</topic><topic>Negative feedback</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Oscillations</topic><topic>Plant cells</topic><topic>Polyploidy</topic><topic>Proliferating cell nuclear antigen</topic><topic>Proliferating Cell Nuclear Antigen - genetics</topic><topic>Proliferating Cell Nuclear Antigen - metabolism</topic><topic>S phase</topic><topic>Transcription</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Minhee</creatorcontrib><creatorcontrib>Delos Santos, Keemo</creatorcontrib><creatorcontrib>Moon, Nam-Sung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Docstoc</collection><collection>University Readers</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genetics (Austin)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Minhee</au><au>Delos Santos, Keemo</au><au>Moon, Nam-Sung</au><au>Duronio, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proper CycE–Cdk2 activity in endocycling tissues requires regulation of the cyclin-dependent kinase inhibitor Dacapo by dE2F1b in Drosophila</atitle><jtitle>Genetics (Austin)</jtitle><addtitle>Genetics</addtitle><date>2021-03-03</date><risdate>2021</risdate><volume>217</volume><issue>1</issue><spage>1</spage><epage>15</epage><pages>1-15</pages><issn>1943-2631</issn><issn>0016-6731</issn><eissn>1943-2631</eissn><abstract>Abstract
Polyploidy is an integral part of development and is associated with cellular stress, aging, and pathological conditions. The endocycle, comprised of successive rounds of G and S phases without mitosis, is widely employed to produce polyploid cells in plants and animals. In Drosophila, maintenance of the endocycle is dependent on E2F-governed oscillations of Cyclin E (CycE)–Cdk2 activity, which is known to be largely regulated at the level of transcription. In this study, we report an additional level of E2F-dependent control of CycE–Cdk2 activity during the endocycle. Genetic experiments revealed that an alternative isoform of Drosophila de2f1, dE2F1b, regulates the expression of the p27CIP/KIP-like Cdk inhibitor Dacapo (Dap). We provide evidence showing that dE2F1b-dependent Dap expression in endocycling tissues is necessary for setting proper CycE–Cdk2 activity. Furthermore, we demonstrate that dE2F1b is required for proliferating cell nuclear antigen expression that establishes a negative feedback loop in S phase. Overall, our study reveals previously unappreciated E2F-dependent regulatory networks that are critical for the periodic transition between G and S phases during the endocycle.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>33683365</pmid><doi>10.1093/genetics/iyaa029</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-8135-645X</orcidid><orcidid>https://orcid.org/0000-0002-0455-927X</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1943-2631 0016-6731 1943-2631 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Aging Animals Antigens Cell Cycle Control theory Cyclin E Cyclin E - genetics Cyclin E - metabolism Cyclin-dependent kinase 2 Cyclin-Dependent Kinase 2 - genetics Cyclin-Dependent Kinase 2 - metabolism Cyclin-dependent kinases Drosophila Drosophila melanogaster Drosophila Proteins - genetics Drosophila Proteins - metabolism E2F protein Enzyme inhibitors Feedback loops Feedback, Physiological Fruit flies Genetics Insects Investigation Kinases Kip protein Mitosis Negative feedback Nuclear Proteins - genetics Nuclear Proteins - metabolism Oscillations Plant cells Polyploidy Proliferating cell nuclear antigen Proliferating Cell Nuclear Antigen - genetics Proliferating Cell Nuclear Antigen - metabolism S phase Transcription Transcription Factors - genetics Transcription Factors - metabolism |
| title | Proper CycE–Cdk2 activity in endocycling tissues requires regulation of the cyclin-dependent kinase inhibitor Dacapo by dE2F1b in Drosophila |
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