Редактирование: CDC25A (раздел)

==Publications==

{{medline-entry
|title=Babam2 Regulates Cell Cycle Progression and Pluripotency in Mouse Embryonic Stem Cells as Revealed by Induced DNA Damage.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33050379
|abstract=BRISC and [[BRCA1]]-A complex member 2 ([i]Babam2[/i]) plays an essential role in promoting cell cycle progression and preventing cellular senescence. [i]Babam2[/i]-deficient fibroblasts show proliferation defect and premature senescence compared with their wild-type (WT) counterpart. Pluripotent mouse embryonic stem cells (mESCs) are known to have unlimited cell proliferation and self-renewal capability without entering cellular senescence. Therefore, studying the role of [i]Babam2[/i] in ESCs would enable us to understand the mechanism of [i]Babam2[/i] in cellular aging, cell cycle regulation, and pluripotency in ESCs. For this study, we generated [i]Babam2[/i] knockout ([i]Babam2[/i] ) mESCs to investigate the function of [i]Babam2[/i] in mESCs. We demonstrated that the loss of [i]Babam2[/i] in mESCs leads to abnormal G1 phase retention in response to DNA damage induced by gamma irradiation or doxorubicin treatments. Key cell cycle regulators, [[CDC25A]] and [[CDK2]], were found to be degraded in [i]Babam2[/i]  mESCs following gamma irradiation. In addition, [i]Babam2[/i]  mESCs expressed p53 strongly and significantly longer than in control mESCs, where p53 inhibited Nanog expression and G1/S cell cycle progression. The combined effects significantly reduced developmental pluripotency in [i]Babam2[/i]  mESCs. In summary, [i]Babam2[/i] maintains cell cycle regulation and pluripotency in mESCs in response to induced DNA damage.

|keywords=* Babam2
* DNA damage
* cell cycle
* embryonic stem cells
* pluripotency
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600899
}}
{{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=Nickel-induced HIF-1α promotes growth arrest and senescence in normal human cells but lacks toxic effects in transformed cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28552779
|abstract=Nickel is a human carcinogen that acts as a hypoxia mimic by activating the transcription factor HIF-1α and hypoxia-like transcriptomic responses. Hypoxia and elevated HIF-1α are typically associated with drug resistance in cancer cells, which is caused by increased drug efflux and other mechanisms. Here we examined the role of HIF-1α in uptake of soluble Ni(II) and Ni(II)-induced cell fate outcomes using si/shRNA knockdowns and gene deletion models. We found that HIF-1α had no effect on accumulation of Ni(II) in two transformed (H460, A549) and two normal human cell lines (IMR90, WI38). The loss of HIF-1α also produced no significant impact on p53-dependent and p53-independent apoptotic responses or clonogenic survival of Ni(II)-treated transformed cells. In normal human cells, HIF-1α enhanced the ability of Ni(II) to inhibit cell proliferation and cause a permanent growth arrest (senescence). Consistent with its growth-suppressive effects, HIF-1α was important for upregulation of the cell cycle inhibitors p21 (CDKN1A) and p27 (CDKN1B). Irrespective of HIF-1α status, Ni(II) strongly increased levels of [[MYC]] protein but did not change protein expression of the cell cycle-promoting phosphatase [[CDC25A]] or the CDK inhibitor p16. Our findings indicate that HIF-1α limits propagation of Ni(II)-damaged normal cells, suggesting that it may act in a tumor suppressor-like manner during early stages of Ni(II) carcinogenesis.
|mesh-terms=* A549 Cells
* Cell Cycle Checkpoints
* Cell Line, Transformed
* Cell Survival
* Cellular Senescence
* Dose-Response Relationship, Drug
* Growth Inhibitors
* Humans
* Hypoxia-Inducible Factor 1, alpha Subunit
* Nickel
|keywords=* Apoptosis
* HIF1A
* Hypoxia
* Nickel
* Senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568485
}}