Редактирование: CDK1

Cyclin-dependent kinase 1 (EC 2.7.11.22) (EC 2.7.11.23) (CDK1) (Cell division control protein 2 homolog) (Cell division protein kinase 1) (p34 protein kinase) [CDC2] [CDC28A] [CDKN1] [P34CDC2]

==Publications==

{{medline-entry
|title=MicroRNAomic Transcriptomic Analysis Reveal Deregulation of Clustered Cellular Functions in Human Mesenchymal Stem Cells During in Vitro Passaging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31848878
|abstract=Clinical trials using human mesenchymal stem/stromal cells (hMSCs) for cell replacement therapy showed varied outcomes, where cells' efficacy has been perceived as the limiting factor. In particular, the quality and number of the expanded cells in vitro. In this study, we aimed to determine molecular signatures of hMSCs derived from the pulp of extracted deciduous teeth (SHED) and Wharton's jelly (WJSCs) that associated with cellular ageing during in vitro passaging. We observed distinct phenotypic changes resembling proliferation reduction, cell enlargement, an increase cell population in G2/M phase, and differentially expressed of tumor suppressor p53 in passage (P) 6 as compared to P3, which indicating in vitro cell senescence. The subsequent molecular analysis showed a set of diverse differentially expressed miRNAs and mRNAs involved in maintaining cell proliferation and stemness properties. Considering the signaling pathway related to G2/M DNA damage regulation is widely recognized as part of anti-proliferation mechanism controlled by p53, we explored possible miRNA-mRNA interaction in this regulatory pathway based on genomic coordinates retrieved from miRanda. Our work reveals the potential reason for SHED underwent proliferation arrest due to the direct impinge on the expression of CKS1 by miRNAs specifically miR-22 and miR-485-5p which lead to down regulation of [[CDK1]] and Cyclin B. It is intended that our study will contribute to the understanding of these miRNA/mRNA driving the biological process and regulating different stages of cell cycle is beneficial in developing effective rejuvenation strategies in order to obtain quality stem cells for transplantation.
|mesh-terms=* CDC2-CDC28 Kinases
* Cell Differentiation
* Cell Proliferation
* Cellular Senescence
* Cyclin B
* Gene Expression Regulation, Developmental
* Humans
* Mesenchymal Stem Cells
* MicroRNAs
* Transcriptome
* Tumor Suppressor Protein p53
* Umbilical Cord
|keywords=* Cell proliferation
* Cell senescence
* Cellular ageing
* Human Mesenchymal stem / stromal cells
* miRNA-mRNA integration
|full-text-url=https://sci-hub.do/10.1007/s12015-019-09924-0
}}
{{medline-entry
|title=Targeting [[DTL]] induces cell cycle arrest and senescence and suppresses cell growth and colony formation through [[TPX2]] inhibition in human hepatocellular carcinoma cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29606879
|abstract=Hepatocellular carcinoma (HCC) has an increasing incidence and high mortality. Surgical operation is not a comprehensive strategy for liver cancer. Moreover, tolerating systemic chemotherapy is difficult for patients with HCC because hepatic function is often impaired due to underlying cirrhosis. Therefore, a comprehensive strategy for cancer treatment should be developed. [[DTL]] (Cdc10-dependent transcript 2) is a critical regulator of cell cycle progression and genomic stability. In our previous study, the upregulation of [[DTL]] expression in aggressive HCC correlated positively with tumor grade and poor patient survival. We hypothesize that targeting [[DTL]] may provide a novel therapeutic strategy for liver cancer. [[DTL]] small interference RNAs were used to knock down [[DTL]] protein expression. A clonogenic assay, immunostaining, double thymidine block, imaging flow cytometry analysis, and a tumor spheroid formation assay were used to analyze the role of [[DTL]] in tumor cell growth, cell cycle progression, micronucleation, ploidy, and tumorigenicity. Our results demonstrated that targeting [[DTL]] reduced cell cycle regulators and chromosome segregation genes, resulting in increased cell micronucleation. [[DTL]] depletion inhibited liver cancer cell growth, increased senescence, and reduced tumorigenesis. [[DTL]] depletion resulted in the disruption of the mitotic proteins cyclin B, [[CDK1]], securin, seprase, Aurora A, and Aurora B as well as the upregulation of the cell cycle arrest gene [i]p21[/i]. A rescue assay indicated that [[DTL]] should be targeted through [[TPX2]] downregulation for cancer cell growth inhibition. Moreover, [[DTL]] silencing inhibited the growth of patient-derived primary cultured HCC cells. Our study results indicate that [[DTL]] is a potential novel target gene for treating liver cancer through liver cancer cell senescence induction. Furthermore, our results provide insights into molecular mechanisms for targeting [[DTL]] in liver cancer cells. The results also indicate several other starting points for future preclinical and clinical studies on liver cancer treatment.

|keywords=* DTL
* TPX2
* cell cycle
* hepatocellular carcinoma
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868578
}}
{{medline-entry
|title=iTRAQ-based proteomic profiling of granulosa cells from lamb and ewe after superstimulation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28708522
|abstract=The number of oocytes obtained from lambs after FSH treatment is far greater than those acquired from adult ewes. However, these oocytes typically have reduced viability in comparison with adult ewe oocytes. However, the molecular mechanisms of differences in viability between lamb and ewe oocytes remain unknown. In the present research, we applied iTRAQ coupled with LC-MS/MS proteomic analysis in order to investigate the proteomic expression profile of granulosa cells from lambs and ewes following stimulation with FSH. We detected 5649 proteins; 574 were differentially expressed between adults and juveniles. Based on Gene Ontology enrichment and KEGG pathway analysis, the majority of DEPs are participated in metabolic processes, ribosome and MAPK signaling pathways. Expression levels in ewes turned out to be lower than lambs. Protein interaction network analysis generated by STRING identified [[MAPK1]], [[SMAD2]], [[SMAD4]], [[CDK1]], [[FOS]] and [[ATM]] as the major findings among 54 significant differentially expressed of proteins. Quantitative real-time PCR analysis was applied to verify the proteomic analysis. These proteins which were identified in lambs may contribute to the reduction of oocyte quality compared to adults. The present research provides understanding of the molecular mechanism for follicle development in lambs.
|mesh-terms=* Aging
* Animals
* Embryo Transfer
* Female
* Fertility
* Fertilization in Vitro
* Follicle Stimulating Hormone
* Granulosa Cells
* Oocytes
* Proteomics
* Real-Time Polymerase Chain Reaction
* Sexual Maturation
* Sheep, Domestic
* Transcriptome
|keywords=* Granulosa cells
* Lamb
* Proteomics
* iTRAQ
|full-text-url=https://sci-hub.do/10.1016/j.theriogenology.2017.06.014
}}
{{medline-entry
|title=[[MYC]] Modulation around the CDK2/p27/SKP2 Axis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28665315
|abstract=[[MYC]] is a pleiotropic transcription factor that controls a number of fundamental cellular processes required for the proliferation and survival of normal and malignant cells, including the cell cycle. [[MYC]] interacts with several central cell cycle regulators that control the balance between cell cycle progression and temporary or permanent cell cycle arrest (cellular senescence). Among these are the cyclin E/A/cyclin-dependent kinase 2 (CDK2) complexes, the CDK inhibitor p27  (p27) and the E3 ubiquitin ligase component S-phase kinase-associated protein 2 (SKP2), which control each other by forming a triangular network. [[MYC]] is engaged in bidirectional crosstalk with each of these players; while [[MYC]] regulates their expression and/or activity, these factors in turn modulate [[MYC]] through protein interactions and post-translational modifications including phosphorylation and ubiquitylation, impacting on [[MYC]]'s transcriptional output on genes involved in cell cycle progression and senescence. Here we elaborate on these network interactions with [[MYC]] and their impact on transcription, cell cycle, replication and stress signaling, and on the role of other players interconnected to this network, such as [[CDK1]], the retinoblastoma protein (pRB), protein phosphatase 2A (PP2A), the F-box proteins [[FBXW7]] and [[FBXO28]], the RAS oncoprotein and the ubiquitin/proteasome system. Finally, we describe how the [[MYC]]/CDK2/p27/SKP2 axis impacts on tumor development and discuss possible ways to interfere therapeutically with this system to improve cancer treatment.

|keywords=* cancer
* cell cycle
* cellular senescence
* oncogenes
* phosphorylation
* post-translational modifications
* protein–protein interactions
* the ubiquitin/proteasome system
* transcription
* tumor suppressor genes
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541307
}}
{{medline-entry
|title=Escape of U251 glioma cells from temozolomide-induced senescence was modulated by [[CDK1]]/survivin signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28559969
|abstract=Temozolomide (TMZ) has been widely used in conjunction with radiotherapy for treating various types of cancers. However, tumor cells arrested in senescence due to TMZ administration can sometimes escape and become drug resistant. In the current study, the possible role of survivin in the senescence escape of TMZ-treated glioma cells was comprehensively studied. The levels of survivin and [[CDK1]] expression in a human glioma cell line (U251) were monitored, and cell apoptosis, cell cycle distribution, anchorage-independent growth, and senescence were studied in U251 cells in different degrees of senescence. To further investigate how survivin affects the TMZ-resistance of gliomas, we modulated the levels of survivin and CKD1 expression in TMZ-treated cells and then examined how the treated cells responded. The results showed that knockdown of the [i]survivin[/i] gene increased the sensitivity of glioma cells to TMZ treatment by inducing senescent cells to become apoptotic. Moreover, after senescence was induced, expression of the [i]survivin[/i] gene became suppressed, but survivin levels returned to normal after the cells had escaped from senescence. While down-regulation of the [i]survivin[/i] gene in senescent and senescence-escaping U251 cells had no effect on cell apoptosis, cell cycle distribution, or senescence status, it dramatically reduced the anchorage-independent growth ability of the cells. Additionally, [[CDK1]] was able to not only enhance the anchorage-independent growth ability of the cells, but also contribute to their further senescence escape by modulating the survivin and other pathways. In conclusion, the [i]survivin[/i] gene was necessary for glioma cells to escape from and enter into senescence during treatment with TMZ.

|keywords=* CDK1
* glioma
* senescence escape
* survivin
* temozolomide
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446501
}}
{{medline-entry
|title=Sperm-associated antigen 9 ([[SPAG9]]) promotes the survival and tumor growth of triple-negative breast cancer cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27449044
|abstract=Recently, we demonstrated the association of sperm-associated antigen 9 ([[SPAG9]]) expression with breast cancer. Among breast cancer, 15 % of the cancers are diagnosed as triple-negative breast cancers (TNBC) based on hormone receptor status and represent an important clinical challenge because of lack of effective available targeted therapy. Therefore, in the present investigation, plasmid-based small hairpin (small hairpin RNA (shRNA)) approach was used to ablate [[SPAG9]] in aggressive breast cancer cell line model (MDA-[[MB]]-231) in order to understand the role of [[SPAG9]] at molecular level in apoptosis, cell cycle, and epithelial-to-mesenchymal transition (EMT) signaling. Our data in MDA-[[MB]]-231 cells showed that ablation of [[SPAG9]] resulted in membrane blebbing, increased mitochondrial membrane potential, DNA fragmentation, phosphatidyl serine surface expression, and caspase activation. [[SPAG9]] depletion also resulted in cell cycle arrest in G0-G1 phase and induced cellular senescence. In addition, in in vitro and in vivo xenograft studies, ablation of [[SPAG9]] resulted in upregulation of p21 along with pro-apoptotic molecules such as BAK, [[BAX]], BIM, [[BID]], NOXA, AIF, Cyto-C, [[PARP1]], [[APAF1]], Caspase 3, and Caspase 9 and epithelial marker, E-cadherin. Also, [[SPAG9]]-depleted cells showed downregulation of cyclin B1, cyclin D1, cyclin E, [[CDK1]], [[CDK4]], [[CDK6]], [[BCL2]], Bcl-xL, [[XIAP]], cIAP2, [[MCL1]], GRP78, SLUG, SNAIL, TWIST, vimentin, N-cadherin, [[MMP2]], [[MMP3]], [[MMP9]], SMA, and β-catenin. Collectively, our data suggests that [[SPAG9]] promotes tumor growth by inhibiting apoptosis, altering cell cycle, and enhancing EMT signaling in in vitro cells and in vivo mouse model. Hence, [[SPAG9]] may be a potential novel target for therapeutic use in TNBC treatment.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Animals
* Apoptosis
* Blotting, Western
* Cell Proliferation
* Fluorescent Antibody Technique, Indirect
* Humans
* Immunoenzyme Techniques
* Membrane Potential, Mitochondrial
* Mice
* RNA, Small Interfering
* Triple Negative Breast Neoplasms
* Tumor Cells, Cultured
|keywords=* Apoptosis
* Cell growth
* Cellular motility
* SPAG9
* Senescence
* Triple-negative breast cancer
* Tumor growth
|full-text-url=https://sci-hub.do/10.1007/s13277-016-5240-6
}}
{{medline-entry
|title=Identification of the lncRNA, AK156230, as a novel regulator of cellular senescence in mouse embryonic fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27343551
|abstract=Long noncoding RNAs (lncRNAs) have gained extensive attentions in recent years because of their potential importance in a variety of biological and pathological processes. In this study, we sought to explore the role of lncRNAs in cellular senescence. Here, we report that the lncRNA AK156230 was downregulated during replicative senescence in mouse embryonic fibroblasts (MEFs), and knockdown of AK156230 promotes a robust senescence phenotype, including increase in the numbers of the senescence-associated β-galactosidase-positive cells, decrease of cell proliferation, accumulation of cells in the G2/M phase and reduction of autophagic activity. The cells with knockdown AK156230 expression also exhibited increased levels of p21, p53 and phosphorylated p53, and a decreased activity of [[CDK1]]. Moreover, rapamycin-induced autophagy offered cytoprotective effect and rescued cellular senescence in AK156230 knockdown cells. Gene expression profile showed that the dysregulation of autophagy and cell cycle genes contributed to the induction of cellular senescence after AK1561230 silencing. Taken together, these results suggest that downregulation of AK156230 is involved in the induction of cellular senescence through its roles in autophagy and cell cycle progression. Our study identifies AK156230 as a critical lncRNA that has a role in regulating cellular senescence in MEFs.
|mesh-terms=* Animals
* Autophagy
* Cell Proliferation
* Cells, Cultured
* Cellular Senescence
* Embryo, Mammalian
* Fibroblasts
* G2 Phase Cell Cycle Checkpoints
* Gene Expression Profiling
* Gene Expression Regulation
* Gene Knockdown Techniques
* Mice, Inbred C57BL
* Phosphorylation
* RNA, Long Noncoding
* Tumor Suppressor Protein p53
|keywords=* AK156230
* Gerotarget
* autophagy
* cellular senescence
* lncRNA
* mouse embryonic fibroblasts
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288140
}}
{{medline-entry
|title=RNA methyltransferase [[NSUN2]] promotes stress-induced HUVEC senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26992231
|abstract=The tRNA methyltransferase [[NSUN2]] delays replicative senescence by regulating the translation of [[CDK1]] and [[CDKN1B]] mRNAs. However, whether [[NSUN2]] influences premature cellular senescence remains untested. Here we show that [[NSUN2]] methylates SHC mRNA in vitro and in cells, thereby enhancing the translation of the three SHC proteins, p66SHC, p52SHC, and p46SHC. Our results further show that the elevation of SHC expression by [[NSUN2]]-mediated mRNA methylation increased the levels of ROS, activated p38MAPK, thereby accelerating oxidative stress- and high-glucose-induced senescence of human vascular endothelial cells (HUVEC). Our findings highlight the critical impact of [[NSUN2]]-mediated mRNA methylation in promoting premature senescence. 
|mesh-terms=* Blotting, Western
* CDC2 Protein Kinase
* Cells, Cultured
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p27
* Gene Expression Regulation
* HCT116 Cells
* Human Umbilical Vein Endothelial Cells
* Humans
* Methylation
* Methyltransferases
* Oxidative Stress
* RNA Interference
* RNA, Messenger
* Reactive Oxygen Species
* Src Homology 2 Domain-Containing, Transforming Protein 1
* p38 Mitogen-Activated Protein Kinases
|keywords=* Gerotarget
* HUVEC
* NSUN2
* SHC mRNA methylation
* premature senescence
* translational regulation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991368
}}
{{medline-entry
|title=Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26765561
|abstract=Rho-associated kinases 1 and 2 ([[ROCK1]]/2) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton, but their role in proliferation and cancer initiation or progression is not known. Here, we provide evidence that [[ROCK1]] and [[ROCK2]] act redundantly to maintain actomyosin contractility and cell proliferation and that their loss leads to cell-cycle arrest and cellular senescence. This phenotype arises from down-regulation of the essential cell-cycle proteins CyclinA, CKS1 and [[CDK1]]. Accordingly, while the loss of either Rock1 or Rock2 had no negative impact on tumorigenesis in mouse models of non-small cell lung cancer and melanoma, loss of both blocked tumor formation, as no tumors arise in which both Rock1 and Rock2 have been genetically deleted. Our results reveal an indispensable role for ROCK, yet redundant role for isoforms 1 and 2, in cell cycle progression and tumorigenesis, possibly through the maintenance of cellular contractility. 
|mesh-terms=* Animals
* Carcinogenesis
* Carcinoma, Non-Small-Cell Lung
* Cell Proliferation
* Gene Knockout Techniques
* Melanoma
* Mice
* rho-Associated Kinases
|keywords=* ROCK
* actin cytoskeleton
* actomyosin contractility
* cancer biology
* cell biology
* cell proliferation
* cellular senescence
* mouse
* rho kinase
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798951
}}
{{medline-entry
|title=NSun2 delays replicative senescence by repressing p27 (KIP1) translation and elevating [[CDK1]] translation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26687548
|abstract=A rise in the levels of the cyclin-dependent kinase (CDK) inhibitor p27KIP1 is important for the growth arrest of senescent cells, but the mechanisms responsible for this increase are poorly understood. Here, we show that the tRNA methyltransferase NSun2 represses the expression of p27 in replicative senescence. NSun2 methylated the 5'-untranslated region (UTR) of p27 mRNA at cytosine C64 in vitro and in cells, thereby repressing the translation of p27. During replicative senescence, increased p27 protein levels were accompanied by decreased NSun2 protein levels. Knockdown of NSun2 in human diploid fibroblasts (HDFs) elevated p27 levels and reduced the expression of [[CDK1]] (encoded by [[CDK1]] mRNA, a previously reported target of NSun2), which in turn further repressed cell proliferation and accelerated replicative senescence, while overexpression of NSun2 exerted the opposite effect. Ectopic overexpression of the p27 5'UTR fragment rescued the effect of NSun2 overexpression in lowering p27, increasing [[CDK1]], promoting cell proliferation, and delaying replicative senescence. Our findings indicate that NSun2-mediated mRNA methylation regulates p27 and [[CDK1]] levels during replicative senescence. 
|mesh-terms=* CDC2 Protein Kinase
* Cell Line
* Cyclin-Dependent Kinase Inhibitor p27
* Cyclin-Dependent Kinases
* Down-Regulation
* Fibroblasts
* Gene Expression Regulation
* Humans
* Methyltransferases
* RNA, Messenger
* Time Factors
|keywords=* NSun2
* mRNA methylation
* p27KIP1
* replicative senescence
* translational regulation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712338
}}
{{medline-entry
|title=Mutant lamin A links prophase to a p53 independent senescence program.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26029982
|abstract=Expression of oncogenes or short telomeres can trigger an anticancer response known as cellular senescence activating the p53 and RB tumor suppressor pathways. This mechanism is switched off in most tumor cells by mutations in p53 and RB signaling pathways. Surprisingly, p53 disabled tumor cells could be forced into senescence by expression of a mutant allele of the nuclear envelope protein lamin A. The pro-senescence lamin A mutant contains a deletion in the sequence required for processing by the protease [[ZMPSTE24]] leading to accumulation of farnesylated lamin A in the nuclear envelope. In addition, the serine at position 22, a target for [[CDK1]]-dependent phosphorylation, was mutated to alanine, preventing [[CDK1]]-catalyzed nuclear envelope disassembly. The accumulation of this mutant lamin A compromised prophase to prometaphase transition leading to invaginations of the nuclear lamina, nuclear fragmentation and impaired chromosome condensation. Cells exited this impaired mitosis without cytokinesis and re-replicated their DNA ultimately arresting in interphase as polyploid cells with features of cellular senescence including increased expression of inflammatory gene products and a significant reduction of tumorigenicity in vivo. 
|mesh-terms=* CDC2 Protein Kinase
* Cell Line, Tumor
* Cell Proliferation
* Cellular Senescence
* Cyclin-Dependent Kinases
* Humans
* Lamin Type A
* Membrane Proteins
* Metalloendopeptidases
* Neoplasms
* Nuclear Envelope
* Phosphorylation
* Retinoblastoma Protein
* Tumor Suppressor Protein p53
|keywords=* ZMPSTE24
* farnesylation
* mitosis
* progeria
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614274
}}
{{medline-entry
|title=Sporadic colorectal cancer development shows rejuvenescence regarding epithelial proliferation and apoptosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24098334
|abstract=Sporadic colorectal cancer (CRC) development is a sequential process showing age-dependency, uncontrolled epithelial proliferation and decreased apoptosis. During juvenile growth cellular proliferation and apoptosis are well balanced, which may be perturbed upon aging. Our aim was to correlate proliferative and apoptotic activities in aging human colonic epithelium and colorectal cancer. We also tested the underlying molecular biology concerning the proliferation- and apoptosis-regulating gene expression alterations. Colorectal biopsies from healthy children (n1 = 14), healthy adults (n2 = 10), adult adenomas (n3 = 10) and CRCs (n4 = 10) in adults were tested for Ki-67 immunohistochemistry and TUNEL apoptosis assay. Mitosis- and apoptosis-related gene expression was also studied in healthy children (n1 = 6), adult (n2 = 41) samples and in CRC (n3 = 34) in HGU133plus2.0 microarray platform. Measured alterations were confirmed with RT-PCR both on dependent and independent sample sets (n1 = 6, n2 = 6, n3 = 6). Mitotic index (MI) was significantly higher (p<0.05) in intact juvenile (MI = 0.33±0.06) and CRC samples (MI = 0.42±0.10) compared to healthy adult samples (MI = 0.15±0.06). In contrast, apoptotic index (AI) was decreased in children (0.13±0.06) and significantly lower in cancer (0.06±0.03) compared to healthy adult samples (0.17±0.05). Eight proliferation- (e.g. [[MKI67]], CCNE1) and 11 apoptosis-associated genes (e.g. [[TNFSF10]], IFI6) had altered mRNA expression both in the course of normal aging and carcinogenesis, mainly inducing proliferation and reducing apoptosis compared to healthy adults. Eight proliferation-associated genes including [[CCND1]], [[CDK1]], [[CDK6]] and 26 apoptosis-regulating genes (e.g. SOCS3) were differently expressed between juvenile and cancer groups mostly supporting the pronounced cell growth in CRC. Colorectal samples from children and CRC patients can be characterized by similarly increased proliferative and decreased apoptotic activities compared to healthy colonic samples from adults. Therefore, cell kinetic alterations during colorectal cancer development show uncontrolled rejuvenescence as opposed to the controlled cell growth in juvenile colonic epithelium.
|mesh-terms=* Adult
* Aging
* Apoptosis
* Carcinogenesis
* Cell Proliferation
* Child
* Colorectal Neoplasms
* Female
* Gene Expression Profiling
* Humans
* Intestinal Mucosa
* Male

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789736
}}
{{medline-entry
|title=Expression profiling of cell cycle genes in human pancreatic islets with and without type 2 diabetes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23707792
|abstract=Microarray gene expression data were used to analyze the expression pattern of cyclin, cyclin-dependent kinase (CDKs) and cyclin-dependent kinase inhibitor (CDKIs) genes from human pancreatic islets with and without type 2 diabetes (T2D). Of the cyclin genes, [[CCNI]] was the most expressed. Data obtained from microarray and qRT-PCR showed higher expression of [[CCND1]] in diabetic islets. Among the CDKs, [[CDK4]], [[CDK8]] and [[CDK9]] were highly expressed, while [[CDK1]] was expressed at low level. High expression of [[[[CDK1]]8]] was observed in diabetic islets. Of the CDKIs, [[CDKN1A]] expression was higher in diabetic islets in both microarray and qRT-PCR. Expression of [[CDKN1A]], [[[[CDKN2A]]]], [[CCNI]]2, [[CDK3]] and [[CDK1]]6 was correlated with age. Finally, eight SNPs in these genes were associated with T2D in the DIAGRAM database. Our data provide a comprehensive expression pattern of cell cycle genes in human islets. More human studies are required to confirm and reproduce animal studies. 
|mesh-terms=* Aged
* Aging
* Case-Control Studies
* Cells, Cultured
* Cyclin-Dependent Kinase Inhibitor Proteins
* Cyclin-Dependent Kinases
* Cyclins
* Diabetes Mellitus, Type 2
* Female
* Gene Expression Profiling
* Genes, cdc
* Genetic Association Studies
* Genetic Predisposition to Disease
* Humans
* Insulin
* Insulin Secretion
* Islets of Langerhans
* Male
* Middle Aged
* Oligonucleotide Array Sequence Analysis
* Polymorphism, Single Nucleotide
* Transcriptome

|full-text-url=https://sci-hub.do/10.1016/j.mce.2013.05.003
}}
{{medline-entry
|title=[[PTOV1]] is associated with UCH-L1 and in response to estrogen stimuli during the mouse oocyte development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21678139
|abstract=To investigate the biological significance of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) involvement in oocyte maturation, we screened for proteins that bound to UCH-L1 in mouse ovaries, and we found that the prostate tumor overexpressed-1 ([[PTOV1]]) protein was able to bind to UCH-L1. [[PTOV1]] is highly expressed in prostate cancers and considered as a potential marker for carcinogenesis and the progress of prostate cancer. It was reported that [[PTOV1]] plays an important role in cell cycle regulation, but its role in mammalian oocyte development and meiosis is still unclear. In this paper, it was found that the expression levels of [[PTOV1]] in mouse ovaries progressively increased from prepubescence to adulthood. And we found by immunohistochemistry that [[PTOV1]] spreaded in both the cytoplasm and nuclei of oocytes during prepuberty, but in normal adult mouse oocytes, it concentrated not only in nuclei but also on the plasma membrane, though in some oocytes with abnormal shapes, [[PTOV1]] did not display the typical distribution patterns. In granulosa cells, however, it was found to locate in the cytoplasm at all the selected ages. In postnatal mouse ovaries (28 days), estradiol treatment induced the adult-specific distribution pattern of [[PTOV1]] in oocytes. In addition, UCH-L1 was shown to be associated with [[CDK1]], which participated in the regulation of cell cycle and oocyte maturation. Therefore, we propose that the distribution changes of [[PTOV1]] are age-dependent, and significant for mouse oocyte development and maturation. Moreover, the discovery that [[PTOV1]] is associated with UCH-L1 in mouse oocytes supports the explanations for that UCH-L1 is involved in oocyte development and maturation, especially under the regulation of estrogen.
|mesh-terms=* Aging
* Animals
* Biomarkers, Tumor
* CDC2 Protein Kinase
* Cell Membrane
* Estradiol
* Estrogens
* Female
* Humans
* Immunohistochemistry
* Male
* Mice
* Neoplasm Proteins
* Oocytes
* Oogenesis
* Ovary
* Tissue Distribution
* Ubiquitin Thiolesterase

|full-text-url=https://sci-hub.do/10.1007/s00418-011-0825-z
}}
{{medline-entry
|title=Expression of second messenger- and cyclin-dependent protein kinases during postnatal development of rat heart.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9620176
|abstract=During early postnatal development, cardiomyocytes, which comprise about 80% of ventricular mass and volume, become phenotypically developed to facilitate their contractile functions and terminally differentiated to grow only in size but not in cell number. These changes are due to the expression of contractile proteins as well as the regulation of intracellular signal transduction proteins. In this study, the expression patterns of several protein kinases involved in various cardiac functions and cell-cycle control were analyzed by Western blotting of ventricular extracts from 1-, 10-, 20-, 50-, and 365-day-old rats. The expression level of cAMP-dependent protein kinase was slightly decreased (20%) over the first year, whereas no change was detected in cGMP-dependent protein kinase I. Calmodulin-dependent protein kinase II, which is involved in Ca2  uptake into the sarcoplasmic reticulum, was increased as much as ten-fold. To the contrary, the expressions of protein kinase C-alpha and iota declined 77% with age. Cyclin-dependent protein kinases (CDKs) such as [[CDK1]], [[CDK2]], [[CDK4]], and [[CDK5]], which are required for cell-cycle progression, abruptly declined to almost undetectable levels after 10-20 days of age. In contrast, other CDK-related kinases, such as [[CDK8]] or Kkialre, did not change significantly or increased up to 50% with age, respectively. Protein kinases implicated in CDK regulation such as [[CDK7]] and Wee1 were either slightly increased in expression or did not change significantly. All of the proteins that were detected in ventricular extracts were also identified in isolated cardiac myocytes in equivalent amounts and analyzed for their relative expression in ten other adult rat tissues.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Blotting, Western
* Calcium-Calmodulin-Dependent Protein Kinase Type 2
* Calcium-Calmodulin-Dependent Protein Kinases
* Cell Cycle Proteins
* Cell Extracts
* Cyclic Nucleotide-Regulated Protein Kinases
* Cyclin-Dependent Kinases
* Heart Ventricles
* Male
* Molecular Sequence Data
* Myocardium
* Nuclear Proteins
* Organ Specificity
* Protein Kinase C
* Protein-Tyrosine Kinases
* Rats
* Rats, Sprague-Dawley
* Second Messenger Systems

|full-text-url=https://sci-hub.do/10.1002/(sici)1097-4644(19980615)69:4<506::aid-jcb11>3.0.co;2-6
}}