Редактирование: CHEK1

Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1) [CHK1]

==Publications==

{{medline-entry
|title=Candesartan Neuroprotection in Rat Primary Neurons Negatively Correlates with Aging and Senescence: a Transcriptomic Analysis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31811565
|abstract=Preclinical experiments and clinical trials demonstrated that angiotensin II AT  receptor overactivity associates with aging and cellular senescence and that AT  receptor blockers (ARBs) protect from age-related brain disorders. In a primary neuronal culture submitted to glutamate excitotoxicity, gene set enrichment analysis (GSEA) revealed expression of several hundred genes altered by glutamate and normalized by candesartan correlated with changes in expression in Alzheimer's patient's hippocampus. To further establish whether our data correlated with gene expression alterations associated with aging and senescence, we compared our global transcriptional data with additional published datasets, including alterations in gene expression in the neocortex and cerebellum of old mice, human frontal cortex after age of 40, gene alterations in the Werner syndrome, rodent caloric restriction, Ras and oncogene-induced senescence in fibroblasts, and to tissues besides the brain such as the muscle and kidney. The most significant and enriched pathways associated with aging and senescence were positively correlated with alterations in gene expression in glutamate-injured neurons and, conversely, negatively correlated when the injured neurons were treated with candesartan. Our results involve multiple genes and pathways, including [[CAV1]], [[CCND1]], [[CDKN1A]], [[CHEK1]], [[ICAM1]], IL-1B, IL-6, [[MAPK14]], [[PTGS2]], [[SERPINE1]], and [[TP53]], encoding proteins associated with aging and senescence hallmarks, such as inflammation, oxidative stress, cell cycle and mitochondrial function alterations, insulin resistance, genomic instability including telomere shortening and DNA damage, and the senescent-associated secretory phenotype. Our results demonstrate that AT  receptor blockade ameliorates central mechanisms of aging and senescence. Using ARBs for prevention and treatment of age-related disorders has important translational value.

|keywords=* Aging
* Angiotensin receptor blockers
* Glutamate excitotoxicity
* Senescence
* p53 neuroprotection
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062590
}}
{{medline-entry
|title=The Ubiquitin-like with PHD and Ring Finger Domains 1 ([[UHRF1]])/DNA Methyltransferase 1 ([[DNMT1]]) Axis Is a Primary Regulator of Cell Senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28100769
|abstract=As senescence develops, cells sequentially acquire diverse senescent phenotypes along with simultaneous multistage gene reprogramming. It remains unclear what acts as the key regulator of the collective changes in gene expression at initiation of senescent reprogramming. Here we analyzed time series gene expression profiles obtained in two different senescence models in human diploid fibroblasts: replicative senescence and H O -induced senescence. Our results demonstrate that suppression of DNA methyltransferase 1 ([[DNMT1]])-mediated DNA methylation activity was an initial event prior to the display of senescent phenotypes. We identified seven [[DNMT1]]-interacting proteins, ubiquitin-like with PHD and ring finger domains 1 ([[UHRF1]]), [[EZH2]], [[CHEK1]], [[SUV39H1]], [[CBX5]], [[PARP1]], and [[HELLS]] (also known as LSH (lymphoid-specific helicase) 1), as being commonly down-regulated at the same time point as [[DNMT1]] in both senescence models. Knockdown experiments revealed that, among the [[DNMT1]]-interacting proteins, only [[UHRF1]] knockdown suppressed [[DNMT1]] transcription. However, [[UHRF1]] overexpression alone did not induce [[DNMT1]] expression, indicating that [[UHRF1]] was essential but not sufficient for [[DNMT1]] transcription. Although [[UHRF1]] knockdown effectively induced senescence, this was significantly attenuated by [[DNMT1]] overexpression, clearly implicating the [[UHRF1]]/[[DNMT1]] axis in senescence. Bioinformatics analysis further identified [[WNT5A]] as a downstream effector of [[UHRF1]]/[[DNMT1]]-mediated senescence. Senescence-associated hypomethylation was found at base pairs -1569 to -1363 from the transcription start site of the [[WNT5A]] gene in senescent human diploid fibroblasts. As expected, [[WNT5A]] overexpression induced senescent phenotypes. Overall, our results indicate that decreased [[UHRF1]] expression is a key initial event in the suppression of [[DNMT1]]-mediated DNA methylation and in the consequent induction of senescence via increasing [[WNT5A]] expression.
|mesh-terms=* CCAAT-Enhancer-Binding Proteins
* Cellular Senescence
* DNA (Cytosine-5-)-Methyltransferase 1
* DNA (Cytosine-5-)-Methyltransferases
* DNA Methylation
* Fibroblasts
* Gene Expression Profiling
* Gene Expression Regulation
* HEK293 Cells
* Histones
* Humans
* Hydrogen Peroxide
* Male
* Oligonucleotide Array Sequence Analysis
* Phenotype
* Promoter Regions, Genetic
* Protein Binding
* Protein Domains
* RNA, Small Interfering
* Ubiquitin-Protein Ligases
* Wnt-5a Protein
* beta-Galactosidase
|keywords=* DNA methylation
* cellular senescence
* gene expression
* gene regulation
* microarray
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339756
}}
{{medline-entry
|title=Aging alters tissue resident mesenchymal stem cell properties.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22265741
|abstract=Tissue resident mesenchymal stem cells (MSCs) are known to participate in tissue regeneration that follows cell turnover, apoptosis, or necrosis. It has been long known that aging impedes an organism's repair/regeneration capabilities. In order to study the age associated changes, the molecular characteristics of adipose tissue derived MSCs (ASCs) from three age groups of healthy volunteers, i.e., young, middle aged, and aged were investigated. The number and multilineage differentiation potential of ASCs declined with age. Aging reduces the proliferative capacity along with increases in cellular senescence. A significant increase in quiescence of G2 and S phase was observed in ASCs from aged donors. The expression of genes related to senescence such as [[CHEK1]] and cyclin-dependent kinase inhibitor p16(ink4a) was increased with age, however genes of apoptosis were downregulated. Further, an age-dependent abnormality in the expression of DNA break repair genes was observed. Global microRNA analysis revealed an abnormal expression of mir-27b, mir-106a, mir-199a, and let-7. In ubiquitously distributed adipose tissue (and ASCs), aging brings about important alterations, which might be critical for tissue regeneration and homeostasis. Our findings therefore provide a better understanding of the mechanism(s) involved in stem cell aging and regenerative potential, and this in turn may affect tissue repair that declines with aging.
|mesh-terms=* Adipose Tissue
* Adolescent
* Adult
* Aged
* Aging
* Apoptosis
* Cell Count
* Cell Cycle
* Cell Differentiation
* Cell Lineage
* Cell Proliferation
* DNA Repair
* Female
* Gene Expression Regulation, Developmental
* Humans
* Male
* Mesenchymal Stem Cells
* MicroRNAs
* Middle Aged
* Transcriptome
* Young Adult

|full-text-url=https://sci-hub.do/10.1016/j.scr.2011.11.002
}}
Описание	Что вы вводите	Что вы получаете
Курсив	''Курсивное начертание''	Курсивное начертание
Полужирный	'''Полужирное начертание'''	Полужирное начертание
Полужирный курсив	'''''Полужирный курсив'''''	Полужирный курсив