Nip2/centrobin may be a substrate of Nek2 that is required for proper spindle assembly during mitosis in early mouse embryos

Sonn, Seongkeun; Jeong, Yeong-Ho; Rhee, Kunsoo

doi:10.1002/mrd.20990

Cited by 20 publications

(19 citation statements)

References 21 publications

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“…Consistent with this, Centrobindepleted cells were arrested in metaphase, as shown by live cell imaging, with a large proportion of cells undergoing mitotic catastrophe as they were unable to resolve the cause of the arrest. This is consistent with mouse studies showing that Centrobin-suppressed embryos were arrested at four-cell stage with mitotic defects in the blastomeres (Sonn et al, 2009).…”

Section: Discussionsupporting

confidence: 92%

Centrobin regulates the assembly of functional mitotic spindles

et al. 2010

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The proper function of the spindle is crucial to the high fidelity of chromosome segregation and is indispensable for tumor suppression in humans. Centrobin is a recently identified centrosomal protein that has a role in stabilizing the microtubule structure. Here we functionally characterize the defects in centrosome integrity and spindle assembly in Centrobin-depleted cells. Centrobin-depleted cells show a range of spindle abnormalities including unfocused poles that are not associated with centrosomes, S-shaped spindles and mini spindles. These cells undergo mitotic arrest and subsequently often die by apoptosis, as determined by live cell imaging. Co-depletion of Mad2 relieves the mitotic arrest, indicating that cells arrest due to a failure to silence the spindle checkpoint in metaphase. Consistent with this, Centrobin-depleted metaphase cells stained positive for BubR1 and BubR1 S676. Staining with a panel of centrosome markers showed a loss of centrosome anchoring to the mitotic spindle. Furthermore, these cells show less cold-stable microtubules and a shorter distance between kinetochore pairs. These results show a requirement of Centrobin in maintaining centrosome integrity, which in turn promotes anchoring of mitotic spindle to the centrosomes. Furthermore, this anchoring is required for the stability of microtubulekinetochore attachments and biogenesis of tension-ridden and properly functioning mitotic spindle.

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Section: Discussionsupporting

confidence: 92%

Centrobin regulates the assembly of functional mitotic spindles

et al. 2010

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“…This is supported by analysis of deletion mutants of CNTROB in HeLa and 293T cells [14,15]. Regarding the importance of the centrosome for mitosis, and in light of a recent study showing a requirement of centrobin for spindle assembly during early embryogenesis [23], it is interesting that the hd mutant fibroblasts in cell culture did not show a proliferation defect. However, it is possible that the truncated centrobin may exert only slight or tissue-specific effects on proliferation.…”

Section: Insertion Of An Endogenous Retrovirus Into Cntrob Gene Causementioning

confidence: 83%

RathdMutation Reveals an Essential Role of Centrobin in Spermatid Head Shaping and Assembly of the Head-Tail Coupling Apparatus1

Liška

Gösele

Rivkin³

et al. 2009

Biology of Reproduction

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The hypodactylous (hd) locus impairs limb development and spermatogenesis, leading to male infertility in rats. We show that the hd mutation is caused by an insertion of an endogenous retrovirus into intron 10 of the Cntrob gene. The retroviral insertion in hd mutant rats disrupts the normal splicing of Cntrob transcripts and results in the expression of a truncated protein. During the final phase of spermiogenesis, centrobin localizes to the manchette, centrosome, and the marginal ring of the spermatid acroplaxome, where it interacts with keratin 5-containing intermediate filaments. Mutant spermatids show a defective acroplaxome marginal ring and separation of the centrosome from its normal attachment site of the nucleus. This separation correlates with a disruption of head-tail coupling apparatus, leading to spermatid decapitation during the final step of spermiogenesis and the absence of sperm in the epididymis. Cntrob may represent a novel candidate gene for presently unexplained hereditary forms of teratozoospermia and the "easily decapitated sperm syndrome" in humans.

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“…NEK2 regulates the mitotic centrosome separation through reversible phosphorylation of its substrates c-NAP1 (Fry et al, 1998), protein phosphatase 1 (PP1) (Helps et al, 2000), NIP1/centrobin (Sonn et al, 2008), β-catenin (Bahmanyar et al, 2008) and SGO1 (Fu et al, 2007) in yeast. In our study, we performed co-immunoprecipitation (CO-IP) and mass spectrometry in cancer cells to identify NEK2 binding proteins.…”

Section: Resultsmentioning

confidence: 99%

NEK2 Induces Drug Resistance Mainly through Activation of Efflux Drug Pumps and Is Associated with Poor Prognosis in Myeloma and Other Cancers

et al. 2013

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SUMMARY Using sequential gene expression profiling (GEP) samples, we defined a major functional group related to drug resistance that contains chromosomal instability (CIN) genes. One CIN gene in particular, NEK2, was highly correlated with drug resistance, rapid relapse, and poor outcome in multiple cancers. Over-expressing NEK2 in cancer cells resulted in enhanced CIN, cell proliferation and drug resistance, while targeting NEK2 by NEK2 shRNA overcame cancer cell drug resistance and induced apoptosis in vitro and in a xenograft myeloma mouse model. High expression of NEK2 induced drug resistance mainly through activation of the efflux pumps. Thus, NEK2 represents a strong predictor for drug resistance and poor prognosis in cancer and could be an important target for cancer therapy.

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Nip2/centrobin may be a substrate of Nek2 that is required for proper spindle assembly during mitosis in early mouse embryos

Cited by 20 publications

References 21 publications

Centrobin regulates the assembly of functional mitotic spindles

Centrobin regulates the assembly of functional mitotic spindles

RathdMutation Reveals an Essential Role of Centrobin in Spermatid Head Shaping and Assembly of the Head-Tail Coupling Apparatus1

NEK2 Induces Drug Resistance Mainly through Activation of Efflux Drug Pumps and Is Associated with Poor Prognosis in Myeloma and Other Cancers

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