Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.

Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs). Activation of the cyclin B-cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/...

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Autores principales:	Natalia Y Boynak, Federico Rojas, Cecilia D'Alessio, Salomé C Vilchez Larrea, Vanina Rodriguez, Pablo D Ghiringhelli, María T Téllez-Iñón
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd2d2596f28f4d1db7ec6ff0737c42de
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spelling	oai:doaj.org-article:cd2d2596f28f4d1db7ec6ff0737c42de2021-11-18T08:48:18ZIdentification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.1932-620310.1371/journal.pone.0079364https://doaj.org/article/cd2d2596f28f4d1db7ec6ff0737c42de2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24223931/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs). Activation of the cyclin B-cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/M transition and inhibits mitotic entry by phosphorylating the inhibitory tyrosine 15 on the cdc2 M-phase-inducing kinase. Wee1 degradation is essential for the exit from the G2 phase. In trypanosomatids, little is known about the genes that regulate cyclin B-cdc2 complexes at the G2/M transition of their cell cycle. Although canonical tyrosine kinases are absent in the genome of trypanosomatids, phosphorylation on protein tyrosine residues has been reported in Trypanosoma brucei. Here, we characterized a Wee1-like protein kinase gene from T. brucei. Expression of TbWee1 in a Schizosaccharomyces pombe strain null for Wee1 inhibited cell division and caused cell elongation. This demonstrates the lengthening of G2, which provided cells with extra time to grow before dividing. The Wee1-like protein kinase was expressed in the procyclic and bloodstream proliferative slender forms of T. brucei and the role of Wee1 in cell cycle progression was analyzed by generating RNA interference cell lines. In the procyclic form of T. brucei, the knock-down of TbWee1 expression by RNAi led to inhibition of parasite growth. Abnormal phenotypes showing an increase in the percentage of cells with 1N0K, 0N1K and 2N1K were observed in these RNAi cell lines. Using parasites with a synchronized cell cycle, we demonstrated that TbWee1 is linked to the G2/M phase. We also showed that TbWee1 is an essential gene necessary for proper cell cycle progression and parasite growth in T. brucei. Our results provide evidence for the existence of a functional Wee1 in T. brucei with a potential role in cell division at G2/M.Natalia Y BoynakFederico RojasCecilia D'AlessioSalomé C Vilchez LarreaVanina RodriguezPablo D GhiringhelliMaría T Téllez-IñónPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79364 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natalia Y Boynak Federico Rojas Cecilia D'Alessio Salomé C Vilchez Larrea Vanina Rodriguez Pablo D Ghiringhelli María T Téllez-Iñón Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.
description	Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs). Activation of the cyclin B-cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/M transition and inhibits mitotic entry by phosphorylating the inhibitory tyrosine 15 on the cdc2 M-phase-inducing kinase. Wee1 degradation is essential for the exit from the G2 phase. In trypanosomatids, little is known about the genes that regulate cyclin B-cdc2 complexes at the G2/M transition of their cell cycle. Although canonical tyrosine kinases are absent in the genome of trypanosomatids, phosphorylation on protein tyrosine residues has been reported in Trypanosoma brucei. Here, we characterized a Wee1-like protein kinase gene from T. brucei. Expression of TbWee1 in a Schizosaccharomyces pombe strain null for Wee1 inhibited cell division and caused cell elongation. This demonstrates the lengthening of G2, which provided cells with extra time to grow before dividing. The Wee1-like protein kinase was expressed in the procyclic and bloodstream proliferative slender forms of T. brucei and the role of Wee1 in cell cycle progression was analyzed by generating RNA interference cell lines. In the procyclic form of T. brucei, the knock-down of TbWee1 expression by RNAi led to inhibition of parasite growth. Abnormal phenotypes showing an increase in the percentage of cells with 1N0K, 0N1K and 2N1K were observed in these RNAi cell lines. Using parasites with a synchronized cell cycle, we demonstrated that TbWee1 is linked to the G2/M phase. We also showed that TbWee1 is an essential gene necessary for proper cell cycle progression and parasite growth in T. brucei. Our results provide evidence for the existence of a functional Wee1 in T. brucei with a potential role in cell division at G2/M.
format	article
author	Natalia Y Boynak Federico Rojas Cecilia D'Alessio Salomé C Vilchez Larrea Vanina Rodriguez Pablo D Ghiringhelli María T Téllez-Iñón
author_facet	Natalia Y Boynak Federico Rojas Cecilia D'Alessio Salomé C Vilchez Larrea Vanina Rodriguez Pablo D Ghiringhelli María T Téllez-Iñón
author_sort	Natalia Y Boynak
title	Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.
title_short	Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.
title_full	Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.
title_fullStr	Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.
title_full_unstemmed	Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.
title_sort	identification of a wee1-like kinase gene essential for procyclic trypanosoma brucei survival.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/cd2d2596f28f4d1db7ec6ff0737c42de
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Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.

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