Assay and Functional Properties of Rabkinesin‐6/Rab6‐KIFL/MKlp2 in Cytokinesis

Neef, Rüdiger; Grüneberg, Ulrike; Barr, Francis A.

doi:10.1016/s0076-6879(05)03054-5

Cited by 21 publications

(24 citation statements)

References 10 publications

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“…The three repressed genes (KIF20A, PSRC1 and CDCA3) have not previously been shown to be responsive to radiation damage. KIF20A is a kinesin involved in chromosome segregation and mitosis (70, 71). CDCA3 is a trigger of mitotic entry (72–75).…”

Section: Discussionmentioning

confidence: 99%

Identification of Radiation-Induced Expression Changes in Nonimmortalized Human T Cells

et al. 2010

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In the event of a radiation accident or attack, it will be imperative to quickly assess the amount of radiation exposure to accurately triage victims for appropriate care. RNA-based radiation dosimetry assays offer the potential to rapidly screen thousands of individuals in an efficient and cost-effective manner. However, prior to the development of these assays, it will be critical to identify those genes that will be most useful to delineate different radiation doses. Using global expression profiling, we examined expression changes in nonimmortalized T cells across a wide range of doses (0.15–12 Gy). Because many radiation responses are highly dependent on time, expression changes were examined at three different times (3, 8, and 24 h). Analyses identified 61, 512 and 1310 genes with significant linear dose-dependent expression changes at 3, 8 and 24 h, respectively. Using a stepwise regression procedure, a model was developed to estimate in vitro radiation exposures using the expression of three genes (CDKN1A, PSRC1 and TNFSF4) and validated in an independent test set with 86% accuracy. These findings suggest that RNA-based expression assays for a small subset of genes can be employed to develop clinical biodosimetry assays to be used in assessments of radiation exposure and toxicity.

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Section: Discussionmentioning

confidence: 99%

Identification of Radiation-Induced Expression Changes in Nonimmortalized Human T Cells

et al. 2010

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“…Hence to understand the mechanism of cytokinesis failure in Seh1-depleted cells we examined the organization of the central spindle and midbody components in anaphase and telophase cells. MKLP2 is a mitotic kinesin-like protein responsible for the spatial restriction of Aurora B to the central spindle (Gruneberg et al, 2004;Neef et al, 2005). MKLP1 is a kinesin-6 family motor protein that becomes activated in anaphase by Aurora B phosphorylation, when cleavage furrow ingression occurs, and is essential for cytokinesis (Neef et al, 2006).…”

Section: Organization Of the Spindle Midzone Region Depends On Seh1mentioning

confidence: 99%

The Nup107-160 Nucleoporin Complex Promotes Mitotic Events via Control of the Localization State of the Chromosome Passenger Complex

Platani

Santarella-Mellwig

Posch

et al. 2009

MBoC

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The human Nup107-160 nucleoporin complex plays a major role in formation of the nuclear pore complex and is localized to kinetochores in mitosis. Here we report that Seh1, a component of the Nup107-160 complex, functions in chromosome alignment and segregation by regulating the centromeric localization of Aurora B and other chromosome passenger complex proteins. Localization of CENP-E is not affected by Seh1 depletion and analysis by electron microscopy showed that microtubule kinetochore attachments are intact. Seh1-depleted cells show impaired Aurora B localization, which results in severe defects in biorientation and organization of the spindle midzone and midbody. Our results indicate that a major function of the Nup107 complex in mitosis is to ensure the proper localization of the CPC at the centromere. INTRODUCTIONThe nuclear envelope (NE) forms the interface between the nucleus and the cytoplasm of the interphase eukaryotic cell and is essential to maintain the unique identity of each compartment. Transport between the two compartments takes place via the nuclear pore complexes (NPCs) of which there are several thousand in vertebrate somatic cells (Allen et al., 2000;Conti and Izaurralde, 2001). Each NPC contains multiple subunits of ϳ30 proteins called nucleoporins (Nups;Cronshaw et al., 2002). In higher eukaryotes NPCs are stable throughout interphase (Daigle et al., 2001), but during mitosis both the nuclear envelope and NPC undergo major structural reorganization. Starting early in prometaphase, breakdown of the nuclear envelope occurs, including disassembly of the nuclear lamina and NPCs. The nuclear envelope membrane proteins and the transmembrane nucleoporins relocalize to the endoplasmic reticulum (ER), whereas the rest of the nuclear envelope and NPC components become distributed throughout the mitotic cytoplasm (Antonin et al., 2008).During mitosis, two complete sets of chromosomes are delivered to a pair of daughter cells. Segregation of each sister chromatid pair is achieved by a highly orchestrated process that requires attachment of the sister kinetochores of each chromosome to microtubules emanating from opposite spindle poles. Kinetochores are protein structures that assemble on chromosome regions known as centromeres and mediate microtubule attachment, mitotic checkpoint signaling, and force generation (Maiato et al., 2004;Tanaka et al., 2005;Cheeseman and Desai, 2008). Electron microscopy (EM) has provided information regarding the structure of vertebrate kinetochores and has led to the division of kinetochores into three distinct regions: the inner kinetochore that associates with chromatin, the outer kinetochore that interacts with spindle microtubules, and the less dense middle kinetochore region (McEwen et al., 2007). Multiple different MT-associated proteins function at kinetochores to form a core attachment site between kinetochore and MTs, with the KMN network (KNL-1/Mis12/NDC80 complex) being the major structural component (Cheeseman et al., 2006). Functional analysis of the NDC8...

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“…It was first identified to function in the dynamics of the Golgi apparatus through interaction with the Rab6A/B GTPase. Moreover, it has been reported that KIF20A is overexpressed in melanoma,11 bladder cancer,10,12 breast cancer,13–15 and pancreatic cancer 16. Knockdown of KIF20A in pancreatic cancer cells can significantly inhibit cell proliferation,17,18 indicating the significance of its overexpression in human cancers.…”

Section: Introductionmentioning

confidence: 99%

“…Kinesin family member 20A (KIF20A), also known as RAB6KIFL, plays an important role in cytokinesis 9,10. It was first identified to function in the dynamics of the Golgi apparatus through interaction with the Rab6A/B GTPase.…”

Section: Introductionmentioning

confidence: 99%

Positive expression of KIF20A indicates poor prognosis of glioma patients

Duan

Huang

2016

OTT

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Glioma patients have a poor overall survival; however, patients can show distinct clinical outcomes due to the high heterogeneity of the tumor, which may be indicated by certain clinicobiological parameters. Kinesin family member 20A (KIF20A), which participates in cytokinesis and intracellular transportation, has been recently reported to be upregulated in pancreatic cancer, breast cancer, and bladder cancer. In the current study, we investigated the expression of KIF20A in gliomas and its significance in predicting the prognosis after surgery. We found that KIF20A positive expression in glioma tissues correlated significantly with Ki67 protein expression and advanced World Health Organization grade. Univariate and multivariate analysis revealed that KIF20A can act as an independent prognostic factor for predicting the overall survival of glioma patients. Moreover, we demonstrated that KIF20A can positively regulate the expression of Ki67 in glioma cell lines. Correspondingly, overexpression of KIF20A can promote cell proliferation and invasion, whereas knockdown of KIF20A can inhibit cell viability and invasion capacity. In vitro study also showed that under the treatment of plumbagin, an anticancer drug, KIF20A expression decreased in a dose-dependent manner. In addition, the overexpression of KIF20A can also increase the drug resistance toward plumbagin, which provided the possibility that KIF20A may contribute to the chemotherapy resistance of gliomas.

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Assay and Functional Properties of Rabkinesin‐6/Rab6‐KIFL/MKlp2 in Cytokinesis

Cited by 21 publications

References 10 publications

Identification of Radiation-Induced Expression Changes in Nonimmortalized Human T Cells

Identification of Radiation-Induced Expression Changes in Nonimmortalized Human T Cells

The Nup107-160 Nucleoporin Complex Promotes Mitotic Events via Control of the Localization State of the Chromosome Passenger Complex

Positive expression of KIF20A indicates poor prognosis of glioma patients

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