Phosphorylation of the centrosomal protein, Cep169, by Cdk1 promotes its dissociation from centrosomes in mitosis

Mori, Yusuke; Inoue, Yoko; Taniyama, Yuki; Tanaka, Sayori; Terada, Yasuhiko

doi:10.1016/j.bbrc.2015.11.004

Cited by 13 publications

(11 citation statements)

References 11 publications

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“…CDK1 modulates the centrosome and mitotic cells, which play important roles in the control of the eukaryotic cell cycle. The CDK1/cyclin A complex controls G2, whereas the CDK1/cyclin B complex governs orderly G2/M transition (i.e., entry into mitosis and maintenance of the mitotic state) [38]. As a key regulator of the cell cycle, CDK1 is a potent therapeutic target for inhibitors in cancer treatment.…”

Section: E919953-8mentioning

confidence: 99%

Comprehensive Analysis of Differential Gene Expression to Identify Common Gene Signatures in Multiple Cancers

et al. 2020

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Background:With the development of research on cancer genomics and microenvironment, a new era of oncology focusing on the complicated gene regulation of pan-cancer research and cancer immunotherapy is emerging. This study aimed to identify the common gene expression characteristics of multiple cancers -lung cancer, liver cancer, kidney cancer, cervical cancer, and breast cancer -and the potential therapeutic targets in public databases. Material/Methods:Gene expression analysis of GSE42568, GSE19188, GSE121248, GSE63514, and GSE66272 in the GEO database of multitype cancers revealed differentially expressed genes (DEGs). Then, GO analysis, KEGG function, and path enrichment analyses were performed. Hub-genes were identified by using the degree of association of protein interaction networks. Moreover, the expression of hub-genes in cancers was verified, and hub-generelated survival analysis was conducted. Finally, infiltration levels of tumor immune cells with related genes were explored. Results:We found 12 cross DEGs in the 5 databases (screening conditions: "adj p<0.05" and "logFC>2 or logFC<-2"). The biological processes of DEGs were mainly concentrated in cell division, regulation of chromosome segregation, nuclear division, cell cycle checkpoint, and mitotic nuclear division. Furthermore, 10 hub-genes were obtained using Cytoscape: TOP2A, ECT2, RRM2, ANLN, NEK2, ASPM, BUB1B, CDK1, DTL, and PRC1. The high expression levels of the 10 genes were associated with the poor survival of these multiple cancers, as well as ASPM, may be associated with immune cell infiltration. Conclusions:Analysis of the common DEGs of multiple cancers showed that 10 hub-genes, especially ASPM and CDK1, can become potential therapeutic targets. This study can serve as a reference to understand the characteristics of different cancers, design basket clinical trials, and create personalized treatments.

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Section: E919953-8mentioning

confidence: 99%

Comprehensive Analysis of Differential Gene Expression to Identify Common Gene Signatures in Multiple Cancers

et al. 2020

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“…Purvalanol A is a selective inhibitor of Cdc2, which strongly inhibits Cdc2 kinase activity at a low concentration of 2 µM (6,7). Investigators have identified that purvalanol A effectively suppresses Cdc2 activity and the progression from the G2 phase to mitosis, which leads to the loss of clonogenicity and cellular apoptosis in both MKN45 and MKN28 X-irradiated gastric cancer cells (8).…”

Section: Introductionmentioning

confidence: 99%

The Cdc2/Cdk1 inhibitor, purvalanol A, enhances the cytotoxic effects of taxol through Op18/stathmin in non-small cell lung cancer cells in vitro

Chen

Liao

Long

et al. 2017

International Journal of Molecular Medicine

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Purvalanol A is a highly selective inhibitor of Cdc2 [also known as cyclin-dependent kinase 1 (CDK1)]. Taxol is an anti-tumor chemotherapeutic drug which is widely used clinically. In this study, the CDK1 inhibitor, purvalanol A was applied to explore the relevance of Cdc2 signaling and taxol sensitivity through analyses, such as cellular proliferation and apoptosis assays, ELISA, western blot analysis and immunoprecipitation. We demonstrated that purvalanol A effectively enhanced the taxol-induced apoptosis of NCI-H1299 cells, as well as its inhibitory effects on cellular proliferation and colony formation. In combination, purvalanol A and taxol mainly decreased the expression of oncoprotein 18 (Op18)/stathmin and phosphorylation at Ser16 and Ser38, while purvalanol A alone inhibited the phosphorylation of Op18/stathmin at all 4 serine sites. Co-treatment with purvalanol A and taxol weakened the expression of Bcl-2 and activated the extrinsic cell death pathway through the activation of caspase-3 and caspase-8. Further experiments indicated that Cdc2 kinase activities, including the expression of Cdc2 and the level of phospho-Cdc2 (Thr161) were significantly higher in taxol-resistant NCI-H1299 cells compared with the relatively sensitive CNE1 cells before and following treatment with taxol. These findings suggest that Cdc2 is positively associatd with the development of taxol resistance. The Cdc2 inhibitor, purvalanol A, enhanced the cytotoxic effects of taxol through Op18/stathmin. Our findings may prove to be useful in clinical practice, as they may provide a treatment strategy with which to to reduce the doses of taxol applied clinically, thus alleviating the side-effects.

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“… 32 , 33 , 34 CDK1 interacts with various cyclins to regulate the cell cycle by regulating the centrosome cycle, mitotic onset, G2‐M transition, G1 progression, and G1‐S transition. 35 , 36 It phosphorylates p53. 37 , 38 CDK1 can substitute other CDKs and is sufficient to drive the mammalian cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis of potential biomarkers for pancreatic cancer

Shi

Chai

et al. 2022

Clinical Laboratory Analysis

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Background Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDA), is an aggressive malignancy associated with a low 5‐year survival rate. Poor outcomes associated with PDA are attributable to late detection and inoperability. Most patients with PDA are diagnosed with locally advanced and metastatic disease. Such cases are primarily treated with chemotherapy and radiotherapy. Because of the lack of effective molecular targets, early diagnosis and successful therapies are limited. The purpose of this study was to screen key candidate genes for PDA using a bioinformatic approach and to research their potential functional, pathway mechanisms associated with PDA progression. It may help to understand the role of associated genes in the development and progression of PDA and identify relevant molecular markers with value for early diagnosis and targeted therapy. Materials and methods To identify novel genes associated with carcinogenesis and progression of PDA, we analyzed the microarray datasets http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62165, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE125158, and http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71989 from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein‐protein interaction (PPI) network was constructed using STRING, and module analysis was performed using Cytoscape. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the differential expression of hub genes in patients with PDA. In addition, we verified the expression of these genes in PDA cell lines and normal pancreatic epithelial cells. Results A total of 202 DEGs were identified and these were found to be enriched for various functions and pathways, including cell adhesion, leukocyte migration, extracellular matrix organization, extracellular region, collagen trimer, membrane raft, fibronectin‐binding, integrin binding, protein digestion, and absorption, and focal adhesion. Among these DEGs, 12 hub genes with high degrees of connectivity were selected. Survival analysis showed that the hub genes (HMMR, CEP55, CDK1, UHRF1, ASPM, RAD51AP1, DLGAP5, KIF11, SHCBP1, PBK, and HMGB2) may be involved in the tumorigenesis and development of PDA, highlighting their potential as diagnostic and therapeutic factors in PDA. Conclusions In summary, the DEGs and hub genes identified in the present study not only contribute to a better understanding of the molecular mechanisms underlying the carcinogenesis and progression of PDA but may also serve as potential new biomarkers and targets for PDA.

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Phosphorylation of the centrosomal protein, Cep169, by Cdk1 promotes its dissociation from centrosomes in mitosis

Cited by 13 publications

References 11 publications

Comprehensive Analysis of Differential Gene Expression to Identify Common Gene Signatures in Multiple Cancers

Comprehensive Analysis of Differential Gene Expression to Identify Common Gene Signatures in Multiple Cancers

The Cdc2/Cdk1 inhibitor, purvalanol A, enhances the cytotoxic effects of taxol through Op18/stathmin in non-small cell lung cancer cells in vitro

Integrated bioinformatics analysis of potential biomarkers for pancreatic cancer

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