Multitasking Ska in Chromosome Segregation: Its Distinct Pools Might Specify Various Functions

Chen, Yujue; Yang, Lu; Liu, Hong

doi:10.1002/bies.201700176

Cited by 10 publications

(13 citation statements)

References 58 publications

(121 reference statements)

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“…However, the impact on the activity of Mps1 itself was not determined, and therefore PP1-Ska could either inhibit Mps1 activity, dephosphorylate the Knl1-MELT motifs, or target both Mps1 and Knl1 (Figure 3I ). The Ska complex binds directly to the Ndc80 complex, although it is currently unclear whether this is mediated by the Ndc80 tail region, CH domain, or the coiled-coil regions of Ndc80 and Nuf2 (Zhang et al, 2012 , 2018 ; Cheerambathur et al, 2017 ; Janczyk et al, 2017 ; Helgeson et al, 2018 ). In fact, the presence of multiple discrete binding interfaces, has prompted others to speculate that Ska may be present in different subcomplexes bound to Ndc80 (Zhang et al, 2018 ).…”

Section: Indirect Effects Of Microtubule Attachments On the Sacmentioning

confidence: 99%

“…The Ska complex binds directly to the Ndc80 complex, although it is currently unclear whether this is mediated by the Ndc80 tail region, CH domain, or the coiled-coil regions of Ndc80 and Nuf2 (Zhang et al, 2012 , 2018 ; Cheerambathur et al, 2017 ; Janczyk et al, 2017 ; Helgeson et al, 2018 ). In fact, the presence of multiple discrete binding interfaces, has prompted others to speculate that Ska may be present in different subcomplexes bound to Ndc80 (Zhang et al, 2018 ). Irrespective of whether these subcomplexes exist, it is likely that the PP1-Ska complex is well positioned to regulate Mps1 activity or localization, since Mps1 binds to the CH domains in Ndc80/Nuf2 (Nijenhuis et al, 2013 ; Hiruma et al, 2015 ; Ji et al, 2015 ).…”

Section: Indirect Effects Of Microtubule Attachments On the Sacmentioning

confidence: 99%

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Kinase and Phosphatase Cross-Talk at the Kinetochore

Saurin

2018

Front. Cell Dev. Biol.

122

137

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Multiple kinases and phosphatases act on the kinetochore to control chromosome segregation: Aurora B, Mps1, Bub1, Plk1, Cdk1, PP1, and PP2A-B56, have all been shown to regulate both kinetochore-microtubule attachments and the spindle assembly checkpoint. Given that so many kinases and phosphatases converge onto two key mitotic processes, it is perhaps not surprising to learn that they are, quite literally, entangled in cross-talk. Inhibition of any one of these enzymes produces secondary effects on all the others, which results in a complicated picture that is very difficult to interpret. This review aims to clarify this picture by first collating the direct effects of each enzyme into one overarching schematic of regulation at the Knl1/Mis12/Ndc80 (KMN) network (a major signaling hub at the outer kinetochore). This schematic will then be used to discuss the implications of the cross-talk that connects these enzymes; both in terms of why it may be needed to produce the right type of kinetochore signals and why it nevertheless complicates our interpretations about which enzymes control what processes. Finally, some general experimental approaches will be discussed that could help to characterize kinetochore signaling by dissociating the direct from indirect effect of kinase or phosphatase inhibition in vivo. Together, this review should provide a framework to help understand how a network of kinases and phosphatases cooperate to regulate two key mitotic processes.

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Section: Indirect Effects Of Microtubule Attachments On the Sacmentioning

confidence: 99%

Section: Indirect Effects Of Microtubule Attachments On the Sacmentioning

confidence: 99%

Kinase and Phosphatase Cross-Talk at the Kinetochore

Saurin

2018

Front. Cell Dev. Biol.

122

137

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“…Ska complex loading to kinetochores requires the NDC80 complex (Gaitanos et al, 2009;Welburn et al, 2009;Chan et al, 2012;Zhang et al, 2012), and the two complexes directly interact (Zhang et al, 2017;Helgeson et al, 2018;Huis in't Veld et al, 2019). Although Ska3 is known to mediate the interaction, its binding site on the NDC80 complex remains unresolved (Zhang et al, 2018). Our results demonstrate that the Hec1 tail is not required for Ska complex-mediated enhancement of NDC80-microtubule interactions or for Ska complex localization to kinetochores in cells.…”

Section: Hec1 Tail Domainmentioning

confidence: 69%

Coordination of NDC80 and Ska complexes at the kinetochore-microtubule interface in human cells

Wimbish

DeLuca

Mick

et al. 2019

Preprint

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The conserved kinetochore-associated NDC80 complex (comprised of Hec1/Ndc80, Nuf2, Spc24, and Spc25) has well-documented roles in mitosis including (1) connecting mitotic chromosomes to spindle microtubules to establish force-transducing kinetochore-microtubule attachments, and (2) regulating the binding strength between kinetochores and microtubules such that correct attachments are stabilized and erroneous attachments are released. Although the NDC80 complex plays a central role in forming and regulating attachments to microtubules, additional factors support these processes as well, including the spindle and kinetochore-associated (Ska) complex. Multiple lines of evidence suggest that Ska complexes strengthen attachments by increasing the ability of NDC80 complexes to bind microtubules, especially to depolymerizing microtubule plus-ends, but how this is accomplished remains unclear. Using cell-based and in vitro assays, we demonstrate that the Hec1 tail domain is dispensable for Ska complex recruitment to kinetochores and for generation of kinetochore-microtubule attachments in human cells. We further demonstrate that Hec1 tail phosphorylation regulates kinetochoremicrotubule attachment stability independently of the Ska complex. Finally, we map the location of the Ska complex in cells to a region near the coiled-coil domain of the NDC80 complex, and demonstrate that this region is required for Ska complex recruitment to the NDC80 complexmicrotubule interface. however, is required for high affinity binding of NDC80 complexes to microtubules in vitro (Wei et al., 2007; Ciferri et al., 2008;Miller et al., 2008; Lampert et al., 2013;Umbreit et al., 2012; Alushin et al., 2012; Cheerambathur et al., 2013;Zaytsev et al., 2015), suggesting that cellular factors likely compensate for Hec1 tail domain functions to varying degrees in different organisms.In addition to generating attachments to spindle microtubules, kinetochores also regulate their stability. In early mitosis attachments are labile and undergo rapid turnover, whereas in late mitosis,

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“…SKA3 is one of the important cyclins. Although some studies have suggested that SKA3 could in uence the progression of certain cancers [22,23], the mechanism underlying its role is still largely unclear and controversial [24][25][26]. Herein, we explored the relationship between SKA3 and the diagnosis and prognosis of HCC and PAAD.…”

Section: Discussionmentioning

confidence: 99%

Expression of Spindle and Kinetochore-related Complex Subunit 3 is Associate With the Progression and Prognosis of Hepatocellular Carcinoma and Pancreatic Adenocarcinoma

Su¹,

Huang²,

Xie³

et al. 2020

Preprint

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Abstract Background Several studies have shown that Spindle and Kinetochore-related Complex Subunit 3 (SKA3) is closely related to the diagnosis and prognosis of various cancers. SKA3 plays a vital role in mitosis, but the mechanism underlying its action in tumors has not been fully elucidated. Methods Two separate microarrays of pancreatic adenocarcinoma (PAAD) and hepatocellular carcinoma (HCC) samples were downloaded from the Gene Expression Omnibus (GEO) and analyzed using R software. Tissues from 203 HCC and 321 PAAD patients were used for tissue microarray (TMA) construction and immunohistochemical staining for scoring. Kaplan-Meier estimators were used to determine their clinical relevance. Finally, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) were used for analyzed rich pathways of SKA3 to understand gene function further. Results Contrary to the results obtained from the GEO database, HCC and PAAD tumor tissues exhibited significantly lower expression of SKA3 compared to the adjacent tissues (P < 0.001). The size of HCC tumor and Edmondson grade were statistically correlated with SKA3 expression (P < 0.05). No correlation was observed between the levels of SKA3 expression and vascular invasion, metastasis, or lymphatic infiltration in HCC patients. Moreover, factors related to decreases of SKA3 in PAAD could similarly not be found. Kaplan-Meier survival curves indicated that SKA3 upregulation in HCC was significantly associated with better prognosis (P = 0.016). In contrast, low levels of SKA3 were related to poor prognosis of PAAD patients (P = 0.026). Enrichment analysis of GO and KEGG pathways showed that SKA3 gene was closely related to cell cycle pathways. Conclusions The results of the present study indicate that SKA3 expression can serve as a diagnostic and prognostic biomarker for HCC and PAAD. However, there is a need to conduct further studies to verify these findings, especially the prognostic role of SKA3 in PAAD.

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Multitasking Ska in Chromosome Segregation: Its Distinct Pools Might Specify Various Functions

Cited by 10 publications

References 58 publications

Kinase and Phosphatase Cross-Talk at the Kinetochore

Kinase and Phosphatase Cross-Talk at the Kinetochore

Coordination of NDC80 and Ska complexes at the kinetochore-microtubule interface in human cells

Expression of Spindle and Kinetochore-related Complex Subunit 3 is Associate With the Progression and Prognosis of Hepatocellular Carcinoma and Pancreatic Adenocarcinoma

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