Редактирование: NEK2

Serine/threonine-protein kinase Nek2 (EC 2.7.11.1) (HSPK 21) (Never in mitosis A-related kinase 2) (NimA-related protein kinase 2) (NimA-like protein kinase 1) [NEK2A] [NLK1]

==Publications==

{{medline-entry
|title=A multidimensional systems biology analysis of cellular senescence in aging and disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32264951
|abstract=Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, [[CDC25A]], [[CDCA4]], [[CKAP2]], [[GTF3C4]], [[HAUS4]], [[IMMT]], [[MCM7]], [[MTHFD2]], [[MYBL2]], [[NEK2]], [[NIPA2]], and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.

|keywords=* Biogerontology
* Cancer
* Genetics
* Longevity
* Transcriptome
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333371
}}
{{medline-entry
|title=Upregulation of [[FOXM1]] leads to diminished drug sensitivity in myeloma.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30463534
|abstract=Following up on previous work demonstrating the involvement of the transcription factor forkhead box M1 ([[FOXM1]]) in the biology and outcome of a high-risk subset of newly diagnosed multiple myeloma (nMM), this study evaluated whether [[FOXM1]] gene expression may be further upregulated upon tumor recurrence in patients with relapsed multiple myeloma (rMM). Also assessed was the hypothesis that increased levels of [[FOXM1]] diminish the sensitivity of myeloma cells to commonly used myeloma drugs, such as the proteasome inhibitor bortezomib (Bz) and the DNA intercalator doxorubicin (Dox). [[FOXM1]] message was evaluated in 88 paired myeloma samples from patients with nMM and rMM, using gene expression microarrays as measurement tool. Sources of differential gene expression were identified and outlier analyses were performed using statistical methods. Two independent human myeloma cell lines (HMCLs) containing normal levels of [[FOXM1]] ([[FOXM1]] ) or elevated levels of lentivirus-encoded [[FOXM1]] ([[FOXM1]] ) were employed to determine [[FOXM1]]-dependent changes in cell proliferation, survival, efflux-pump activity, and drug sensitivity. Levels of retinoblastoma (Rb) protein were determined with the assistance of Western blotting. Upregulation of [[FOXM1]] occurred in 61 of 88 (69%) patients with rMM, including 4 patients that exhibited > 20-fold elevated expression peaks. Increased [[FOXM1]] levels in [[FOXM1]]  myeloma cells caused partial resistance to Bz (1.9-5.6 fold) and Dox (1.5-2.9 fold) in vitro, using [[FOXM1]]  myeloma as control. Reduced sensitivity of [[FOXM1]]  cells to Bz was confirmed in vivo using myeloma-in-mouse xenografts. [[FOXM1]]-dependent regulation of total and phosphorylated Rb agreed with a working model of myeloma suggesting that [[FOXM1]] governs both chromosomal instability (CIN) and E2F-dependent proliferation, using a mechanism that involves interaction with NIMA related kinase 2 ([[NEK2]]) and cyclin dependent kinase 6 (CDK6), respectively. These findings enhanced our understanding of the emerging [[FOXM1]] genetic network in myeloma and provided preclinical support for the therapeutic targeting of the [[FOXM1]]-[[NEK2]] and CDK4/6-Rb-E2F pathways using small-drug CDK and [[NEK2]] inhibitors. Clinical research is warranted to assess whether this approach may overcome drug resistance in [[FOXM1]]  myeloma and, thereby, improve the outcome of patients in which the transcription factor is expressed at high levels.
|mesh-terms=* Animals
* Antineoplastic Agents
* Bortezomib
* Cell Line, Tumor
* Cell Proliferation
* Cell Survival
* Doxorubicin
* Drug Resistance
* Drug Tolerance
* Forkhead Box Protein M1
* Gene Expression Profiling
* Gene Expression Regulation, Neoplastic
* Humans
* Mice, Inbred NOD
* Mice, Knockout
* Mice, SCID
* Multiple Myeloma
* Up-Regulation
* Xenograft Model Antitumor Assays
|keywords=* Cellular senescence
* Plasma-cell neoplasm
* Small-drug inhibitor
* Targeted cancer therapy
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249818
}}