Plk1 phosphorylation of CAP-H2 triggers chromosome condensation by condensin II at the early phase of mitosis

Kagami, Yuya; Ono, M.; Yoshida, Kiyotsugu

doi:10.1038/s41598-017-05986-7

Cited by 23 publications

(23 citation statements)

References 27 publications

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“…In A. thaliana, this interaction is likely not conserved, since we could not detect RBR among the proteins that co-purified with CAP-D3. In human, Cdc20, a component of the anaphase-promoting complex E3 ubiquitin ligase, interacts and regulates CAP-H2 (Kagami et al, 2017). In Drosophila, CAP-H2 also interacts and is regulated by the Skp cullin-F-box SCF Slimb (Buster et al, 2013), an E3 ubiquitin ligase regulated by CSN (Hotton and Callis, 2008).…”

Section: The Subunit Composition Of Arabidopsis Condensin I and Ii Ismentioning

confidence: 99%

The Arabidopsis condensin CAP-D subunits arrange interphase chromatin

Municio

Antosz

Grasser

et al. 2019

Preprint

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Condensins are best known for their role in shaping chromosomes. However, other functions as organizing interphase chromatin and transcriptional control have been reported in yeasts and animals. Yeasts encode one condensin complex, while higher eukaryotes have two of them (condensin I and II). Both, condensin I and II, are conserved in Arabidopsis thaliana, but so far little is known about their function. Here we show that the A. thaliana CAP-D2 (condensin I) and CAP-D3 (condensin II) subunits are highly expressed in mitotically active tissues. In silico and pull-down experiments indicate that both CAP-D proteins interact with the other condensin I and II subunits. Our data suggest that the expression, localization and composition of the condensin complexes in A. thaliana are similar as in other higher eukaryotes. Previous experiments showed that the lack of A. thaliana CAP-D3 leads to centromere association during interphase. To study the function of CAP-D3 in chromatin organization more in detail we compared the nuclear distribution of rDNA, of centromeric chromocenters and of different epigenetic marks, as well as the nuclear size between wild-type and cap-d3 mutants. In these mutants an association of heterochromatic sequences occurs, but nuclear size and the general methylation and acetylation patterns remain unchanged. In addition, transcriptome analyses revealed a moderate influence of CAP-D3 on general transcription, but a stronger one on transcription of stress-related genes. We propose a model for the CAP-D3 function during interphase, where CAP-D3 localizes in euchromatin loops to stiff them, and consequently separates centromeric regions and 45S rDNA repeats.

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Section: The Subunit Composition Of Arabidopsis Condensin I and Ii Ismentioning

confidence: 99%

The Arabidopsis condensin CAP-D subunits arrange interphase chromatin

Municio

Antosz

Grasser

et al. 2019

Preprint

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“…Activation of condensin II by Cdk1-mediated phosphorylation is based on that chromosome condensation takes place before the nuclear envelope breakdown in cells depleted of Plk1 activity [ 47 ]. Recently, Kagami et al [ 48 ] shows Plk1 phosphorylation of hCAP-H2 at Ser288 also triggers chromosome condensation at the early phase of mitosis. But the molecular mechanism in their report is different from that of mitotic chromosome condensation caused by phosphorylation of hCAP-D3 [ 46 ].…”

Section: Multiple Cellular Functions and Regulations Of Human Condensmentioning

confidence: 99%

“…The protein levels of hCAP-H2 are increased in mitosis by a Plk1 kinase activity-dependent manner. Inhibition of Plk1 induces cell-division cycle protein 20 (Cdc20)-mediated degradation of hCAP-H2 [ 48 ].…”

Section: Multiple Cellular Functions and Regulations Of Human Condensmentioning

confidence: 99%

Subunits of human condensins are potential therapeutic targets for cancers

Wang

Yang

et al. 2018

Cell Div

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The main role of condensins is to regulate chromosome condensation and segregation during cell cycles. Recently, it has been suggested in the literatures that subunits of condensin I and condensin II are involved in some human cancers. This paper will first briefly discuss discoveries of human condensins, their components and structures, and their multiple cellular functions. This will be followed by reviews of most recent studies on subunits of human condensins and their dysregulations or mutations in human cancers. It can be concluded that many of these subunits have potentials to be novel targets for cancer therapies. However, hCAP-D2, a subunit of human condensin I, has not been directly documented to be associated with any human cancers to date. This review hypothesizes that hCAP-D2 can also be a potential therapeutic target for human cancers, and therefore that all subunits of human condensins are potential therapeutic targets for human cancers.Electronic supplementary materialThe online version of this article (10.1186/s13008-018-0035-3) contains supplementary material, which is available to authorized users.

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“…Condensin I is present in interphase, while condensin II is active in mitotic cells. PLK1 regulates the levels of the CAP-H2 component in condensin II in early mitosis by phosphorylating CAP-H2 and protects condensin II from APC/C degradation [ 82 ]. Dysregulation of condensin II through PLK1 inhibition leads to anaphase segregation defects such as lagging chromosomes [ 82 ].…”

Section: Role Of Plk1 During Mitosis and Cytokinesismentioning

confidence: 99%

“…PLK1 regulates the levels of the CAP-H2 component in condensin II in early mitosis by phosphorylating CAP-H2 and protects condensin II from APC/C degradation [ 82 ]. Dysregulation of condensin II through PLK1 inhibition leads to anaphase segregation defects such as lagging chromosomes [ 82 ]. PLK1 also binds to condensin II through CAP-D3, which is primed by the initial CDK1-dependent phosphorylation, to promote further phosphorylation and condensin II activity [ 83 ].…”

Section: Role Of Plk1 During Mitosis and Cytokinesismentioning

confidence: 99%

The CINs of Polo-Like Kinase 1 in Cancer

Cunningham

MacAuley

Vizeacoumar

et al. 2020

Cancers

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Polo-like kinase 1 (PLK1) is overexpressed near ubiquitously across all cancer types and dysregulation of this enzyme is closely tied to increased chromosomal instability and tumor heterogeneity. PLK1 is a mitotic kinase with a critical role in maintaining chromosomal integrity through its function in processes ranging from the mitotic checkpoint, centrosome biogenesis, bipolar spindle formation, chromosome segregation, DNA replication licensing, DNA damage repair, and cytokinesis. The relation between dysregulated PLK1 and chromosomal instability (CIN) makes it an attractive target for cancer therapy. However, clinical trials with PLK1 inhibitors as cancer drugs have generally displayed poor responses or adverse side-effects. This is in part because targeting CIN regulators, including PLK1, can elevate CIN to lethal levels in normal cells, affecting normal physiology. Nevertheless, aiming at related genetic interactions, such as synthetic dosage lethal (SDL) interactions of PLK1 instead of PLK1 itself, can help to avoid the detrimental side effects associated with increased levels of CIN. Since PLK1 overexpression contributes to tumor heterogeneity, targeting SDL interactions may also provide an effective strategy to suppressing this malignant phenotype in a personalized fashion.

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Plk1 phosphorylation of CAP-H2 triggers chromosome condensation by condensin II at the early phase of mitosis

Cited by 23 publications

References 27 publications

The Arabidopsis condensin CAP-D subunits arrange interphase chromatin

The Arabidopsis condensin CAP-D subunits arrange interphase chromatin

Subunits of human condensins are potential therapeutic targets for cancers

The CINs of Polo-Like Kinase 1 in Cancer

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