Редактирование: CCNA2

Cyclin-A2 (Cyclin-A) (Cyclin A) [CCN1] [CCNA]

==Publications==

{{medline-entry
|title=Hepatoprotective effects of hydroxysafflor yellow A in D-galactose-treated aging mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32454116
|abstract=Hydroxysafflor yellow A (HSYA) is an effective chemical component isolated from Chinese herb Carthamus tinctorius L. In present study, we aimed to evaluate the effects of HSYA on D-galactose- (D-gal-) induced aging in mice, and to elucidate the underlying mechanism. Male C57BL/6 mice were intraperitoneal injection of D-gal and HSYA for 8 weeks. The body weight gain, spleen and thymus coefficients were determined. Levels of super dismutase (SOD), catalase ([[CAT]]), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in serum and liver were measured using commercial kits. Pathological changes and the SA-β-Gal activity in liver tissues were detected by hematoxylin and eosin and SA-β-Gal staining. The expression levels of p16, [[CDK4]], [[CDK6]] and phosphorylation levels of Retinoblastoma (Rb) were detected by immunohistochemistry and western blot analysis. mRNA levels of genes regulated by p16-Rb pathway were determined by quantitative real-time PCR. In vivo, HSYA improved the aging changes including body weight, organ index and antioxidant status such as activities of SOD, [[CAT]], GSH-Px and MDA in D-gal treated aging mice. HSYA also dramatically attenuated pathologic changes of aging liver tissues induced by D-gal. Furthermore, HSYA significantly decreased the mRNA and protein level of cyclin-dependent kinase inhibitor p16, followed by increasing [[CDK4]]/6 protein expression and decreasing the phosphorylation of Retinoblastoma (pRb) which up-regulated the expression of downstream genes [[CCNE1]], [[CCNA2]], P107 and [[MCM4]]. Collectively, these data indicated that HSYA could ameliorate aging, especially hepatic replicative senescence resulting from D-gal, the mechanism could be associated with the suppression of p16-Rb pathway.

|keywords=* D-galactose
* Hydroxysafflor yellow A
* Oxidative stress
* Replicative senescence
* p16
|full-text-url=https://sci-hub.do/10.1016/j.ejphar.2020.173214
}}
{{medline-entry
|title=Hypoxia Upregulates Mitotic Cyclins Which Contribute to the Multipotency of Human Mesenchymal Stem Cells by Expanding Proliferation Lifespan.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29463071
|abstract=Hypoxic culture is widely recognized as a method to efficiently expand human mesenchymal stem cells ([[MSC]]s) without loss of stem cell properties. However, the molecular basis of how hypoxia priming benefits [[MSC]] expansion remains unclear. In this report, our systemic quantitative proteomic and RT-PCR analyses revealed the involvement of hypoxic conditioning activated genes in the signaling process of the mitotic cell cycle. Introduction of screened two mitotic cyclins, [[CCNA2]] and [[CCNB1]], significantly extended the proliferation lifespan of [[MSC]]s in normoxic condition. Our results provide important molecular evidence that multipotency of human [[MSC]]s by hypoxic conditioning is determined by the mitotic cell cycle duration. Thus, the activation of mitotic cyclins could be a potential strategy to the application of stem cell therapy.
|mesh-terms=* Cell Differentiation
* Cell Hypoxia
* Cell Proliferation
* Humans
* Mesenchymal Stem Cells
* Up-Regulation
|keywords=* cell proliferation lifespan
* cyclin
* human mesenchymal stem cell
* hypoxia
* mitosis
* multipotency
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881094
}}
{{medline-entry
|title=Cyclin A2 promotes DNA repair in the brain during both development and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27425845
|abstract=Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation in[[CCNA2]]-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that [[CCNA2]]-null progenitors thus experienced lengthened cell cycle. We demonstrate that [[CCNA2]]-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal [[CCNA2]] ablation results in learning and memory deficits in aged mice.
|mesh-terms=* Aging
* Animals
* Behavior, Animal
* Brain
* Cell Cycle
* Conditioning, Psychological
* Cyclin A2
* DNA Repair
* Hand Strength
* Mice
* Mice, Transgenic
* Models, Biological
* Motor Skills
* Neurons
* Social Behavior
* Stem Cell Niche
|keywords=* Cyclin A2
* DNA repair
* mathematical modeling
* neural stem cells
* ventricular zone/subventricular zone
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993346
}}
{{medline-entry
|title=PIM-1 modulates cellular senescence and links IL-6 signaling to heterochromatin formation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25040935
|abstract=Cellular senescence is a stable state of proliferative arrest that provides a barrier against malignant transformation and contributes to the antitumor activity of certain chemotherapies. Unexpectedly, we found that the expression of proto-oncogene PIM-1, which can promote tumorigenesis, is induced at transcriptional level during senescence. Inhibition of PIM-1 alleviated both replicative and oncogene-induced senescence. Conversely, ectopic expression of PIM-1 resulted in premature senescence. We also revealed that PIM-1 interacts with and phosphorylates heterochromatin protein 1γ (HP1γ) on Ser93. This PIM-1-mediated HP1γ phosphorylation enhanced HP1γ's capacity to bind to H3K9me3, resulting in heterochromatin formation and suppression of proliferative genes, such as [[CCNA2]] and PCNA. Analysis of the mechanism underlying the up-regulation of PIM-1 expression during senescence demonstrated that IL-6, a critical regulator of cellular senescence, is responsible for PIM-1 induction. Our study demonstrated that PIM-1 is a key component of the senescence machinery that contributes to heterochromatin formation. More importantly, we demonstrated that PIM-1 is also a direct target of IL-6/STAT3 signaling and mediates cytokine-induced cellular senescence. 
|mesh-terms=* Cellular Senescence
* Fibroblasts
* Heterochromatin
* Humans
* Interleukin-6
* Phosphorylation
* Proto-Oncogene Proteins c-pim-1
* STAT3 Transcription Factor
* Signal Transduction
* Transcriptional Activation
* Up-Regulation
|keywords=* HP1γ
* IL-6
* PIM-1
* STAT3
* senescence
* senescence-associated heterochromatin foci
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331745
}}