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Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number

2013-11-18Journal article Open access
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dc.contributor.authorCunha-Ferreira, Inês
dc.contributor.authorBento, Inês
dc.contributor.authorPimenta-Marques, Ana
dc.contributor.authorJana, Swadhin Chandra
dc.contributor.authorLince-Faria, Mariana
dc.contributor.authorDuarte, Paulo
dc.contributor.authorBorrego-Pinto, Joana
dc.contributor.authorGilberto, Samuel
dc.contributor.authorAmado, Tiago
dc.contributor.authorBrito, Daniela
dc.contributor.authorRodrigues-Martins, Ana
dc.contributor.authorDebski, Janusz
dc.contributor.authorDzhindzhev, Nikola
dc.contributor.authorBettencourt-Dias, Mónica
dc.date.accessioned2018-02-08T17:05:19Z
dc.date.available2018-02-08T17:05:19Z
dc.date.issued2013-11-18
dc.descriptionThe deposited article is a post-print version and has been submitted to peer review.pt_PT
dc.descriptionThis publication hasn't any creative commons license associated.pt_PT
dc.descriptionThis deposit is composed by the main article plus the supplementary materials of the publication.pt_PT
dc.description.abstractPolo-like kinase 4 (PLK4) is a major player in centriole biogenesis: in its absence centrioles fail to form, while in excess leads to centriole amplification. The SCF-Slimb/βTrCP-E3 ubiquitin ligase controls PLK4 levels through recognition of a conserved phosphodegron. SCF-Slimb/βTrCP substrate binding and targeting for degradation is normally regulated by phosphorylation cascades, controlling complex processes, such as circadian clocks and morphogenesis. Here, we show that PLK4 is a suicide kinase, autophosphorylating in residues that are critical for SCF-Slimb/βTrCP binding. We demonstrate a multisite trans-autophosphorylation mechanism, likely to ensure that both a threshold of PLK4 concentration is attained and a sequence of events is observed before PLK4 can autodestruct. First, we show that PLK4 trans-autophosphorylates other PLK4 molecules on both Ser293 and Thr297 within the degron and that these residues contribute differently for PLK4 degradation, the first being critical and the second maximizing auto-destruction. Second, PLK4 trans-autophosphorylates a phospho-cluster outside the degron, which regulates Thr297 phosphorylation, PLK4 degradation, and centriole number. Finally, we show the importance of PLK4-Slimb/βTrCP regulation as it operates in both soma and germline. As βTrCP, PLK4, and centriole number are deregulated in several cancers, our work provides novel links between centriole number control and tumorigenesis.pt_PT
dc.description.sponsorshipFundação para a Ciência e Tecnologia grants: (SFRH/BD/33213/2007, PTDC/SAU-OBD/73194/2006, PTDC/SAU-OBD/105616/2008); ERC grant:(ERC-2010-StG grant number 261344); EMBO installation grant.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInês Cunha-Ferreira, Inês Bento, Ana Pimenta-Marques, Swadhin Chandra Jana, Mariana Lince-Faria, Paulo Duarte, Joana Borrego-Pinto, Samuel Gilberto, Tiago Amado, Daniela Brito, Ana Rodrigues-Martins, Janusz Debski, Nikola Dzhindzhev, Mónica Bettencourt-Dias, Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number, Current Biology, Volume 23, Issue 22, 2013, Pages 2245-2254, ISSN 0960-9822, https://doi.org/10.1016/j.cub.2013.09.037. (http://www.sciencedirect.com/science/article/pii/S0960982213011846)pt_PT
dc.identifier.doi10.1016/j.cub.2013.09.037pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/833
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationPROGRAMA GULBENKIAN DE DOUTORAMENTO
dc.relationRegulation Of The Function Of The Tumourigenesis-Associated Kinase SAK/PLK4
dc.relationControl of Centriole Structure And Number
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0960982213011846?via%3Dihubpt_PT
dc.subjectPLK4pt_PT
dc.subjectCentriolespt_PT
dc.subjectphosphorylationpt_PT
dc.subjectCell Cycle Proteinspt_PT
dc.subjectgeneticspt_PT
dc.subjectDrosophilapt_PT
dc.subjectUbiquitin-Protein Ligasespt_PT
dc.subjectAmino Acid Sequencept_PT
dc.titleRegulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Numberpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePROGRAMA GULBENKIAN DE DOUTORAMENTO
oaire.awardTitleRegulation Of The Function Of The Tumourigenesis-Associated Kinase SAK/PLK4
oaire.awardTitleControl of Centriole Structure And Number
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F33213%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-OBD%2F73194%2F2006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-OBD%2F105616%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/261344/EU
oaire.citation.endPage2254pt_PT
oaire.citation.issue22pt_PT
oaire.citation.startPage2245pt_PT
oaire.citation.titleCurrent Biologypt_PT
oaire.citation.volume23pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationed381816-59b1-4b82-afeb-909de24f40b9
relation.isProjectOfPublication665506fd-76ee-424f-adb1-84f7fa42033b
relation.isProjectOfPublication1848efe2-6ac0-4b9c-a402-c3138611e8d1
relation.isProjectOfPublication0faa6bb2-99b3-4582-9b24-873d528eceb3
relation.isProjectOfPublication.latestForDiscovery0faa6bb2-99b3-4582-9b24-873d528eceb3

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