Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.7/833
Title: Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number
Author: 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
Keywords: PLK4
Centrioles
phosphorylation
Cell Cycle Proteins
genetics
Drosophila
Ubiquitin-Protein Ligases
Amino Acid Sequence
Issue Date: 18-Nov-2013
Publisher: Elsevier
Citation: 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)
Abstract: 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.
Description: The 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.
Peer review: yes
URI: http://hdl.handle.net/10400.7/833
DOI: 10.1016/j.cub.2013.09.037
Publisher Version: https://www.sciencedirect.com/science/article/pii/S0960982213011846?via%3Dihub
Appears in Collections:CCR - Artigos

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