Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2013 |
| Outros Autores: | , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.7/833 |
Resumo: | The deposited article is a post-print version and has been submitted to peer review. |
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Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole NumberPLK4CentriolesphosphorylationCell Cycle ProteinsgeneticsDrosophilaUbiquitin-Protein LigasesAmino Acid SequenceThe deposited article is a post-print version and has been submitted to peer review.This publication hasn't any creative commons license associated.This deposit is composed by the main article plus the supplementary materials of the publication.Polo-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.Fundação 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.ElsevierARCACunha-Ferreira, InêsBento, InêsPimenta-Marques, AnaJana, Swadhin ChandraLince-Faria, MarianaDuarte, PauloBorrego-Pinto, JoanaGilberto, SamuelAmado, TiagoBrito, DanielaRodrigues-Martins, AnaDebski, JanuszDzhindzhev, NikolaBettencourt-Dias, Mónica2018-02-08T17:05:19Z2013-11-182013-11-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.7/833engInês 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)10.1016/j.cub.2013.09.037info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:35:14Zoai:arca.igc.gulbenkian.pt:10400.7/833Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:12:03.201831Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number |
| title |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number |
| spellingShingle |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number Cunha-Ferreira, Inês PLK4 Centrioles phosphorylation Cell Cycle Proteins genetics Drosophila Ubiquitin-Protein Ligases Amino Acid Sequence |
| title_short |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number |
| title_full |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number |
| title_fullStr |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number |
| title_full_unstemmed |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number |
| title_sort |
Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number |
| author |
Cunha-Ferreira, Inês |
| author_facet |
Cunha-Ferreira, Inês Bento, Inês Pimenta-Marques, Ana Jana, Swadhin Chandra Lince-Faria, Mariana Duarte, Paulo Borrego-Pinto, Joana Gilberto, Samuel Amado, Tiago Brito, Daniela Rodrigues-Martins, Ana Debski, Janusz Dzhindzhev, Nikola Bettencourt-Dias, Mónica |
| author_role |
author |
| author2 |
Bento, Inês Pimenta-Marques, Ana Jana, Swadhin Chandra Lince-Faria, Mariana Duarte, Paulo Borrego-Pinto, Joana Gilberto, Samuel Amado, Tiago Brito, Daniela Rodrigues-Martins, Ana Debski, Janusz Dzhindzhev, Nikola Bettencourt-Dias, Mónica |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
ARCA |
| dc.contributor.author.fl_str_mv |
Cunha-Ferreira, Inês Bento, Inês Pimenta-Marques, Ana Jana, Swadhin Chandra Lince-Faria, Mariana Duarte, Paulo Borrego-Pinto, Joana Gilberto, Samuel Amado, Tiago Brito, Daniela Rodrigues-Martins, Ana Debski, Janusz Dzhindzhev, Nikola Bettencourt-Dias, Mónica |
| dc.subject.por.fl_str_mv |
PLK4 Centrioles phosphorylation Cell Cycle Proteins genetics Drosophila Ubiquitin-Protein Ligases Amino Acid Sequence |
| topic |
PLK4 Centrioles phosphorylation Cell Cycle Proteins genetics Drosophila Ubiquitin-Protein Ligases Amino Acid Sequence |
| description |
The deposited article is a post-print version and has been submitted to peer review. |
| publishDate |
2013 |
| dc.date.none.fl_str_mv |
2013-11-18 2013-11-18T00:00:00Z 2018-02-08T17:05:19Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/833 |
| url |
http://hdl.handle.net/10400.7/833 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Inês 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) 10.1016/j.cub.2013.09.037 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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