Characterization of Cep85: A novel antagonist of Nek2A that is involved in the regulation of centrosome disjunction

Chen, Canhe; Tian, Fang; Lü, Lin; Wang, Yun; Xu, Zhe; Chen, Yu; Yu, Xiang

doi:10.1242/jcs.171637

Cited by 18 publications

(26 citation statements)

References 36 publications

(80 reference statements)

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“…For example, NS3 (Fig. 3H) interacts with UNC119B, a myristoyl chaperone required for recruiting NPHP (nephronophthisis) proteins to cilia (56); CEP192, a major regulator of centrosome and spindle assembly; OFD1, a centrosome/centriolar satellite protein (57); and CEP85, a protein linked to centrosome biogenesis (58,59). The NS3-OFD1 interaction was validated via BioID (Fig.…”

Section: Resultsmentioning

confidence: 99%

Global Interactomics Uncovers Extensive Organellar Targeting by Zika Virus

Coyaud

Ranadheera

Cheng

et al. 2018

Molecular & Cellular Proteomics

113

136

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Zika virus (ZIKV) is a membrane enveloped Flavivirus with a positive strand RNA genome, transmitted by mosquitoes. The geographical range of ZIKV has dramatically expanded in recent decades resulting in increasing numbers of infected individuals, and the spike in ZIKV infections has been linked to significant increases in both Guillain-Barré syndrome and microcephaly. Although a large number of host proteins have been physically and/or functionally linked to other Flaviviruses, very little is known about the virus-host protein interactions established by ZIKV. Here we map host cell protein interaction profiles for each of the ten polypeptides encoded in the ZIKV genome, generating a protein topology network comprising 3033 interactions among 1224 unique human polypeptides. The interactome is enriched in proteins with roles in polypeptide processing and quality control, vesicle trafficking, RNA processing and lipid metabolism.>60% of the network components have been previously implicated in other types of viral infections; the remaining interactors comprise hundreds of new putative ZIKV functional partners. Mining this rich data set, we highlight several examples of how ZIKV may usurp or disrupt the function of host cell organelles, and uncover an important role for peroxisomes in ZIKV infection.

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Section: Resultsmentioning

confidence: 99%

Global Interactomics Uncovers Extensive Organellar Targeting by Zika Virus

Coyaud

Ranadheera

Cheng

et al. 2018

Molecular & Cellular Proteomics

113

136

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“…Of five tested interactions, we confirmed three in the pairwise Y2H screen: DCTN6, EFHC, and NEK2. The corresponding functional relationships associated with their centrosome location relate to protein organelle/vesicle transport and spindle morphogenesis (DCTN6 [ 97 ]), microtubule-regulation of cell division (EFHC1 [ 98 ]), and centrosome separation control and bipolar spindle formation (NEK2 [ 99 , 100 ]). Further indications of the potential pleiotropic role of this effector came from the confirmed interactions associated with nucleus-located host proteins involved in transcription via FAM60A in translational repression and the peptidylprolyl isomerase PPIE in the spliceosome.…”

Section: Resultsmentioning

confidence: 99%

Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions

et al. 2017

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Coxiella burnetii is an obligate Gram-negative intracellular pathogen and the etiological agent of Q fever. Successful infection requires a functional Type IV secretion system, which translocates more than 100 effector proteins into the host cytosol to establish the infection, restructure the intracellular host environment, and create a parasitophorous vacuole where the replicating bacteria reside. We used yeast two-hybrid (Y2H) screening of 33 selected C. burnetii effectors against whole genome human and murine proteome libraries to generate a map of potential host-pathogen protein-protein interactions (PPIs). We detected 273 unique interactions between 20 pathogen and 247 human proteins, and 157 between 17 pathogen and 137 murine proteins. We used orthology to combine the data and create a single host-pathogen interaction network containing 415 unique interactions between 25 C. burnetii and 363 human proteins. We further performed complementary pairwise Y2H testing of 43 out of 91 C. burnetii-human interactions involving five pathogen proteins. We used the combined data to 1) perform enrichment analyses of target host cellular processes and pathways, 2) examine effectors with known infection phenotypes, and 3) infer potential mechanisms of action for four effectors with uncharacterized functions. The host-pathogen interaction profiles supported known Coxiella phenotypes, such as adapting cell morphology through cytoskeletal re-arrangements, protein processing and trafficking, organelle generation, cholesterol processing, innate immune modulation, and interactions with the ubiquitin and proteasome pathways. The generated dataset of PPIs—the largest collection of unbiased Coxiella host-pathogen interactions to date—represents a rich source of information with respect to secreted pathogen effector proteins and their interactions with human host proteins.

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“…NEK2 belongs to the CCRK family of cell cycle-regulating proteins and it is a serine/threonine kinase located in the centrosome. [32][33][34] Previous studies have demonstrated that elevation in NEK2 contributes to the regulation of centrosome separation and spindle formation, and to ensuring that the chromosome structure is more stable and complete. 35,36 In cancer-related studies, NEK2 was found to be up-regulated in various types of cancer tissues and cell lines, suggesting the involvement of NEK2 in tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

NIMA-Related Kinase 2 Overexpression is Associated with Poor Survival in Cancer Patients: A Systematic Review and Meta-Analysis

et al. 2018

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NIMA-related kinase 2 (NEK2) has been reported to be overexpressed in various types of cancer and correlated with poor prognosis. The role(s) of NEK2 in cancer, however, is still uncertain. The aim of this study was to evaluate the prognostic value of NEK2 in human tumors. Methods: A comprehensive literature search was performed for PubMed, Embase, Web of Science, and CNKI databases, and eligible studies were included based on the inclusion and exclusion criteria. A meta-analysis of the included studies was then carried out. Results: Fifteen studies with 3,280 cancer patients were included in the present meta-analysis. All publications were of moderate to high quality, and had no significant heterogeneity (I 2=46% , P=0.03) or publication bias was discovered. The results showed that a high NEK2 level was associated with shorter overall survival (OS) in patients with various types of cancers (pooled HR=1.72, 95% CI 1.49-2.00, P<0.00001). However, the disease-free survival (DFS) had no significant association with NEK2 level (HR=1.13, 95% CI: 0.29-4.38, P=0.85). In the subgroup analyses, high NEK2 level was correlated with an increased risk of poor OS in patients with hepatocellular carcinoma (HR=1.62, 95% CI: 1.25-2.10, P=0.02) and lung cancer (HR=2.18, 95% CI: 1.40-3.38, P=0.0005). However, other factors, including sample size, follow-up period, HR estimation method, and country, also affect the association between NEK2 expression and OS. Analysis of clinicopathological parameters further showed that increased NEK2 level was correlated with younger age, male gender, better tumor differentiation, and lower number of tumor nodules. Conclusion: The results of this study indicated that increased expression of NEK2 was associated with unfavorable survival of cancer patients and that NEK2 could be used as a prognostic predictor for cancers.

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Characterization of Cep85: A novel antagonist of Nek2A that is involved in the regulation of centrosome disjunction

Cited by 18 publications

References 36 publications

Global Interactomics Uncovers Extensive Organellar Targeting by Zika Virus

Global Interactomics Uncovers Extensive Organellar Targeting by Zika Virus

Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions

NIMA-Related Kinase 2 Overexpression is Associated with Poor Survival in Cancer Patients: A Systematic Review and Meta-Analysis

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