Cdk1 plays matchmaker for the Polo-like kinase and its activator SPAT-1/Bora

Tavernier, Nicolas; Panbianco, Costanza Viola Sofia; Gotta, Monica; Pintard, Lionel

doi:10.1080/15384101.2015.1053673

Cited by 10 publications

(12 citation statements)

References 43 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When mammalian PLK1 is phosphorylated by AKA, mitosis is initiated in the cells [36]. In addition, cyclin B-CDK1-dependent phosphorylation of aurora borealis is a pre-requisite for PLK activation [37]. GlAK was found in basal bodies (in interphase and dividing cells) and mitotic spindles (in dividing cells), and AK inhibition resulted in a cytokinesis defect [23,38,39].…”

Section: Discussionmentioning

confidence: 99%

A polo-like kinase modulates cytokinesis and flagella biogenesis in Giardia lamblia

Park

Kim

Shin

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Polo-like kinases (PLKs) are conserved serine/threonine kinase, regulating cell cycle. Giardia lamblia PLK (GlPLK) role in its cell has not been yet studied. Here, the function of GlPLK was investigated to provide the insight of roles in Giardia cell division, especially during cytokinesis and in flagella formation. Methods To access the function of GlPLK, Giardia trophozoites were treated with PLK-specific inhibitor, GW843286X (GW) or anti-glplk morpholino, then growth of the cells was monitored and phenotypic characteristics of GlPLK-inhibited cells were observed by using mitotic index and flow cytometry assay. Transgenic G. lamblia expressing GlPLK as a hemagglutinin (HA)-tagging was constructed and used for immunofluorescence assay to detect the localization of GlPLK, followed by the subcellular fractionation. Furthermore, kinase assay was performed to assess the phosphorylation activities of GlPLK by purified proteins or in vitro synthesized proteins. To elucidate the role of phosphorylated GlPLK, the phosphorylation residues were mutated and expressed in Giardia trophozoites. Results After incubating trophozoites with 5 µM GW, the percentages of cells with four nuclei and/or longer flagella were increased. Immunofluorescence assays indicated that GlPLK was mainly localized at basal bodies and transiently localized at mitotic spindles in the dividing cells. Fractionation experiments demonstrated that GlPLK is present in the nuclear fraction, as did the centromeric histone H3. Morpholino-mediated GlPLK knockdown resulted in the same phenotypes as those observed in GW-treated cells, i.e., increased mitotic index and flagella length. Kinase assays using mutant recombinant GlPLKs indicated that mutation at Lys51 or at both Thr179 and Thr183 resulted in loss of kinase activity. Giardia expressing these mutant GlPLKs also demonstrated defects in cell growth, cytokinesis, and flagella. Conclusions These data indicated that GlPLK plays roles in Giardia cell division, especially during cytokinesis, and in flagella formation.

show abstract

Section: Discussionmentioning

confidence: 99%

A polo-like kinase modulates cytokinesis and flagella biogenesis in Giardia lamblia

Park

Kim

Shin

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…(79). In this study, YM-155 mediated a loss of many of these processes including CCNB1 [-2.5, p<0.001] and CCNB2 [-2.77, p<0.001] (which encodes G2/mitotic-specific cyclin-B 1 and 2 proteins) cyclin B/CDK1, BORA, AURKB, CENPA, CCNE2 and its target PLK1 [-2.41, p<0.001], all of which are essential for mitotic recovery after DNA damage (80)(81)(82)(83)(84)(85). Many of these cycle checkpoint transcripts are reportedly overexpressed in aggressive chemo resistant tumors (86)(87)(88)(89)(90)(91) leading to unbridled proliferation (92), poor prognosis (93) to which small-molecule inhibitors that target these kinases are currently being tested as anticancer drugs (94)(95)(96).…”

Section: Discussionmentioning

confidence: 99%

Effects of Sepantronium Bromide (YM-155) on the Whole Transcriptome of MDA-MB-231 Cells: Highlight on Impaired ATR/ATM Fanconi Anemia DNA Damage Response

Mazzio

Lewis

Elhag

et al. 2018

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Sepantronium bromide (YM-155) is believed to elicit apoptosis and mitotic arrest in tumor cells by reducing (BIRC5, survivin) mRNA. In this study, we monitored changes in survivin mRNA and protein after treating MDA-MB-231 cells with YM-155 concurrent with evaluation of whole transcriptomic (WT) mRNA and long intergenic non-coding RNA at 2 time points: 8 h sub-lethal (83 ng/mL) and 20 h at the LC (14.6 ng/mL). The data show a tight association between cell death and the precipitating loss of survivin protein and mRNA (-2.67 fold-change (FC), p<0.001) at 20 h, questioning if the decline in survivin is attributed to cell death or drug impact. The meager loss of survivin mRNA was overshadowed by enormous differential change to the WT in both magnitude and significance for over 2000 differentially up/down-regulated transcripts: (+22 FC to -12 FC, p<0.001). The data show YM-155 to up-regulate transcripts in control of circadian rhythm (NOCT, PER, BHLHe40, NFIL3), tumor suppression (SIK1, FOSB), histone methylation (KDM6B) and negative feedback of NF-kappa B signaling (TNFAIP3). Down-regulated transcripts by YM-155 include glucuronidase (GUSBP3), numerous micro-RNAs, DNA damage repair elements (CENPI, POLQ, RAD54B) and the most affected system was the ataxia-telangiectasia mutated (ATM)/Fanconi anemia E3 monoubiquitin ligase core complexes (FANC transcripts - A/B/E/F/G/M), FANC2, FANCI, BRCA1, BRCA2, RAD51, PALB2 gene and ATR (ATM- and Rad3-Related) pathway. In conclusion, these findings suggest that a primary target of YM-155 is the loss of replicative DNA repair systems.

show abstract

“…During mitotic entry, Polo kinase is activated by phosphorylation of an evolutionarily conserved residue located in the activation loop (Thr210 in human Plk1) [ 29 , 30 ]. Phosphorylation at this residue is primarily mediated by Aurora A in vertebrates ( figure 1 , point 3) [ 31 , 32 ] and possibly also in C. elegans [ 33 , 34 ], and by Aurora B in Drosophila [ 35 ]. Aurora A is enriched at spindle poles, and phosphorylated Plk1 is first detected at centrosomes as human cells enter mitosis [ 10 ].…”

Section: Mechanisms Of Spatio-temporal Regulation Of Polo At the G2/mmentioning

confidence: 99%

“…Bora accumulates at the G2/M transition in human cells and promotes Plk1 phosphorylation by Aurora A [ 31 , 32 ]. Importantly, this function of Bora in Polo activation is greatly stimulated by its phosphorylation by Cyclin–CDK complexes in both human cells and C. elegans [ 33 , 34 , 72 , 73 ]. Cyclin–CDK enzymes phosphorylate Bora at multiple sites but phosphorylation of three evolutionarily conserved residues located in the N-terminal, most conserved part of the protein is critical for Bora function in Polo activation, both in C. elegans embryos and in human cells [ 33 , 72 , 73 ].…”

Section: The Upstream Trigger: Cyclin A–cdk1 Primes Bora For Polo Actmentioning

confidence: 99%

A unified view of spatio-temporal control of mitotic entry: Polo kinase as the key

Pintard

Archambault

2018

Open Biol.

Self Cite

View full text Add to dashboard Cite

The Polo kinase is an essential regulator of cell division. Its ability to regulate multiple events at distinct subcellular locations and times during mitosis is remarkable. In the last few years, a much clearer mechanistic understanding of the functions and regulation of Polo in cell division has emerged. In this regard, the importance of coupling changes in activity with changes in localization is striking, both for Polo itself and for its upstream regulators. This review brings together several new pieces of the puzzle that are gradually revealing how Polo is regulated, in space and time, to enable its functions in the early stages of mitosis in animal cells. As a result, a unified view of how mitotic entry is spatio-temporally regulated is emerging.

show abstract

Cdk1 plays matchmaker for the Polo-like kinase and its activator SPAT-1/Bora

Cited by 10 publications

References 43 publications

A polo-like kinase modulates cytokinesis and flagella biogenesis in Giardia lamblia

A polo-like kinase modulates cytokinesis and flagella biogenesis in Giardia lamblia

Effects of Sepantronium Bromide (YM-155) on the Whole Transcriptome of MDA-MB-231 Cells: Highlight on Impaired ATR/ATM Fanconi Anemia DNA Damage Response

A unified view of spatio-temporal control of mitotic entry: Polo kinase as the key

Contact Info

Product

Resources

About