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Last update 08 May 2025

CENP-E

Last update 08 May 2025

Basic Info

Synonyms

CENP-E, CENPE, Centromere protein E

+ [8]

Introduction

Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation. Drives chromosome congression (alignment of chromosomes at the spindle equator resulting in the formation of the metaphase plate) by mediating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the establishment and maintenance of connections between kinetochores and spindle microtubules (PubMed:23891108, PubMed:25395579, PubMed:7889940). The transport of pole-proximal chromosomes towards the spindle equator is favored by microtubule tracks that are detyrosinated (PubMed:25908662). Acts as a processive bi-directional tracker of dynamic microtubule tips; after chromosomes have congressed, continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends (PubMed:23955301). Suppresses chromosome congression in NDC80-depleted cells and contributes positively to congression only when microtubules are stabilized (PubMed:25743205). Plays an important role in the formation of stable attachments between kinetochores and spindle microtubules (PubMed:17535814) The stabilization of kinetochore-microtubule attachment also requires CENPE-dependent localization of other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays a role in spindle assembly checkpoint activation (SAC) via its interaction with BUB1B resulting in the activation of its kinase activity, which is important for activating SAC. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss (By similarity).

Drugs associated with CENP-E

SSR-250411

Target

CENP-E

Mechanism

CENP-E inhibitors

Active Org.-

Originator Org.

Sanofi SA

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

GSK-923295

Target

CENP-E

Mechanism

CENP-E inhibitors

Active Org.-

Originator Org.

GSK Plc

Active Indication-

Inactive Indication

Recurrent Carcinoma [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SAR-132885

Target

CENP-E x alpha-tubulin

Mechanism

CENP-E inhibitors [+1]

Active Org.-

Originator Org.

Sanofi SA

Active Indication-

Inactive Indication

Solid tumor

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with CENP-E

NCT00504790

/ CompletedPhase 1

A Phase I, Open-Label, Dose-Escalation, First Time in Human Study to Evaluate the Safety Profile, Pharmacokinetics, and Pharmacodynamics of GSK923295 in Subjects With Refractory Cancers

This is a Phase I, open-label, first time in human study of GSK923295, in adult subjects with cancers that do not respond to standard therapy. This study will be conducted in two stages; a dose-escalation stage (Stage 1) and an expansion cohort stage (Stage 2).

Start Date25 Jun 2007

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with CENP-E

100 Translational Medicine associated with CENP-E

0 Patents (Medical) associated with CENP-E

506

Literatures (Medical) associated with CENP-E

02 Apr 2025·The Plant Cell

The kinesin motor POS3 and the microtubule polymerase MOR1 coordinate chromosome congression during mitosis in Arabidopsis

Article

Author: Li, Yuanfeng ; Sheen, Jen ; Li, Shuting ; Shen, Xiao ; Chen, Yu ; Liu, Xiayan ; Lei, Pei ; Wang, Xiaomin ; Zhang, Hongchang ; An, Xue ; Yang, Lan ; Liu, Haofeng ; Yu, Fei

AbstractFaithful chromosome segregation during mitosis is crucial for eukaryotic organisms. Centromere-associated protein-E (CENP-E), a kinetochore-localized kinesin motor, facilitates chromosome congression during mitosis in animals. However, it remains unclear whether plants rely on kinesins similar to CENP-E for chromosome alignment. In our genetic screens for Arabidopsis (Arabidopsis thaliana) mutants that are hypersensitive to the microtubule-destabilizing drug propyzamide, we identified propyzamide oversensitive3-1 (pos3-1), which harbors a mutation in a kinesin-like protein that shares sequence similarity with the N-terminal region of CENP-E. We demonstrated that POS3 dynamically associates with kinetochores during chromosome congression and segregation in mitosis. Moreover, loss of POS3 results in prolonged mitosis, increased aneuploidy, and misaligned chromosomes near the spindle poles. Unexpectedly, we discovered a direct physical interaction and functional link between POS3 and the microtubule polymerase MICROTUBULE ORGANIZATION1 (MOR1) in regulating chromosome alignment and segregation during mitosis. Finally, we showed that MOR1 is required for the kinetochore localization of POS3 in mitosis. Together, our findings establish the vital role of POS3 in chromosome congression and uncover a functional link between POS3 and MOR1 that is essential for proper chromosome alignment and segregation in plant mitosis.

01 Apr 2025·Current Research in Translational Medicine

Identifying potential prognosis markers in relapsed multiple myeloma via integrated bioinformatics analysis and biological experiments

Article

Author: Zhou, He ; Cao, Xinya ; Xu, Yong ; Bai, Hua ; Xu, Han ; Chen, Bing

BACKGROUNDAlmost all multiple myeloma (MM) patients will eventually develop disease that has relapsed with or become refractory to current therapeutic regimes. However, the pervious clinical parameters have been proved inaccurate for defining MM relapse, and molecular targets have become the focuses of interests. Prognostic predictions based on molecular targets have been more effective to this day. Our research was performed to demonstrate hub genes involving relapsed MM by bioinformatics and biological experiments.METHODS AND RESULTSThe integrated bioinformatics analysis in baseline and relapsed MM patients were executed. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were utilized to analyze biologic functions of up-regulated differentially expressed genes (DEGs). Four hub genes (CENPE, ASPM, TOP2A and FANCI) were adopted for construction of relapsed gene score model (RGS), and RGS model was evaluated in two testing sets. The CENPE inhibitor GSK923295 had anti-myeloma effect, including promoting cell death, cell cycle arrest and DNA damage of MM cell lines.CONCLUSIONThrough bioinformatics analysis, we found that the four hub genes (CENPE, ASPM, TOP2A and FANCI) were associated to cell cycle, nuclear division, mitosis and spindle. Our research provided proof-of-concept that RGS model could be utilized to estimate recurrence risk and prognosis for patients, and targeting CENPE contributed to developing novel therapeutic pattern for MM.

24 Mar 2025·Protein & Peptide Letters

Unveiling the Potential Role of Hesperetin and Emodin as a Combination Therapy to Inhibit the Pancreatic Cancer Progression against the C-Met Gene

Article

Author: Kaviyaprabha, Rangaraj ; Muthusami, Sridhar ; Miji, Thandaserry Vasudevan ; Arulselvan, Palanisamy ; Bharathi, Muruganantham ; Sreelakshmi, Puthupparambil Shaji

Background:Pancreatic adenocarcinoma (PAAD) is one of the most prevalent cancers, and it has high death rates. Only 10% of PAAD patients can survive until 5 years. Hence, the improvement of survival rate of the patients should be improved.Aim:The present study used a computational approach to identify novel biomarkers and potentially effective small drug-like molecules in PAAD.Objective:The objective of this study was to identify the Differentially Expressed Genes (DEGs) and survival rate affecting genes (SDEGs) to single out the specific gene responsible for pancreatic cancer and predict the efficacy of interactions with hesperetin and emodin. Further, another objective was to validate the predicted efficacies using an MTT assay.Methods:The GEPIA2 database was used to analyze the TCGA-PAAD dataset and identify DEGs and SDEGs. Venn identified the commonly scattered genes between the DEGs and SDEGs. Network Analyst v3.0, CytoScape v3.10.1, and cytoHubba were used for PPI network construction and hub genes identification was described as target proteins. The PDB and PubChem were utilized to obtain the PDB structure of the target proteins and 13 phytocompounds in SDF format. Molecular docking studies were carried out and visualized by utilizing Autodock vina and Discovery Studio Visualizer v19.1.0.1828. The cytotoxicity was measured in the MiaPaCa-2 cell line after being treated with hesperetin and emodin.Results:A total of 9219 Differentially Expressed Genes (DEGs) from the TCGA-PAAD dataset were identified. Among them, 8740 and 479 genes were up and down-regulated with the statistical significance of P ≤ 0.05, respectively. Likely, 500 most survival rate affecting genes (SDEGs) in PAAD patients with a statistical significance of P ≤ 0.05 were identified. The common 137 genes were identified between these obtained DEGs and SDEGs. The survival heat map was delineated for the predicted 137 common genes. Ninety-six genes were identified as the most hazardous genes (highlighted in red). After that, the network was constructed by using protein-protein interaction (PPI) for the most hazardous 96 genes. From the constructed PPI network, the highly interacted top 10 genes were identified. The survival analysis was carried out to identify the most hazardous genes and revealed that all the identified genes significantly reduced the survival rate of the patients affected by PAAD. From that, high survival affecting 5 genes, such as CDK1, CENPE, NCAPG, KIF20A, and c-MET, were selected for further analysis. The molecular docking studies were carried out for the identified top 5 genes, with the 13 phytocompounds reviewed previously for anti-cancer activity. The molecular docking analysis revealed that the hesperetin (binding affinity (BA) = -8.0 kcal/mol; Root mean square deviation (RMSD) = 2.012 Å) and emodin (BA = -8.6 kcal/mol; RMSD = 1.605 Å) interacted well with the c-MET based on the number of hydrogen bonds and BA. Hence, the synergistic efficacy was validated in the cell line MiaPaCa-2 with the hesperetin, emodin, and hesperetin: emodin in combination and obtained the IC50 values of 171.3 μM, 72.94 μM, and 92.36 μM respectively.Conclusion:The results stated that emodin significantly reduced the cell proliferation rate of the MiaPaCa-2 pancreatic cells, and no synergistic effects were observed in this context with hesperetin. However, emodin improved the hesperetin efficacy in pancreatic cells, indicating that structural modification through pharmacokinetics by coupling these two compounds may help to identify novel compounds to treat pancreatic cancer in the future. However, further pancreatic cell lines, such as Panc-1, Bx- PC-3, etc., and in vivo models that include CDX and PDX are needed to verify the combination effect of hespertin and emodin on pancreatic cells.

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