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Metabolic rate depression during prolonged bouts of torpor is characteristic of mammalian hibernation, reducing energy expenditures over the winter. Cell cycle arrest is observed in quiescent cells during dormancy, partly due to the retinoblastoma (Rb) protein at G1/S, given cell division and proliferation are metabolic‐costly processes. Rb binds to E2F transcription factors and recruits corepressors (e.g., SUV39H1) to E2F target genes, blocking their transcription and cell cycle passage. Phosphorylation by cyclin‐CDK complexes at S780 or S795 abolishes Rb‐mediated repression, allowing transition into S phase. The present study compares Rb‐E2F1 responses between euthermic and torpid states in five organs (brain, heart, kidney, liver, skeletal muscle) of 13‐lined ground squirrels (Ictidomys tridecemlineatus). Immunoblotting assessed the expression of Rb, pRb (S780, S795), E2F1, and SUV39H1. Our findings demonstrate multi‐tissue upregulation of Rb and SUV39H1 during torpor, with tissue‐specific changes to E2F1 and pRb (S780), suggesting Rb‐E2F1 contributes to cell cycle control in hibernation. Highlights: Tissue‐specific regulation of the Rb‐E2F1 pathway in 13‐lined ground squirrel.Rb repress E2F1, and Suv39H1 can act as additional factor in cell cycle repression in brain, kidney and liver.Possibility of alternate of roles of E2F1 in the heart and liver during hibernation. [ABSTRACT FROM AUTHOR]

Abstract: High mobility group (HMG) box‐containing protein 1 (HBP1) is a member of the HMG family of chromosomal proteins. Previous studies have shown that human HBP1 exhibits tumor‐suppressor activity. Here, we identified a homologue of HBP1, L‐hbp1, in Lampetra japonica. The L‐hbp1 gene shared high sequence similarity with its homologues in jawed vertebrates, as shown by bioinformatics analyses. L‐hbp1 contains a 1,584‐bp open reading frame that encodes 527 amino acids. A pAdenox‐L‐HBP1 plasmid was constructed and transfected successfully in Raji cells, as revealed by real‐time PCR. The overexpression of L‐HBP1 reduced cell growth rates, inhibited G1 phase progression, decreased cyclin D1 and c‐Myc protein expression, and increased p53 protein expression. Western blot and immunohistochemical assays showed that L‐HBP1 was primarily distributed in the heart, kidney, gill and liver of lamprey. Cell cycle analysis revealed that decreased L‐HBP1 expression in HBP1 morpholino oligonucleotide‐transfected lamprey cells resulted in a decreased fraction of cells in the G1 phase and corresponding increases in the S and G2/M phases. Additionally, treatment of lamprey cardiac cells with pharmacological inhibitors of p38 MAP kinase released the cells from G1 arrest. Together, these results indicated that HBP1 expression in lamprey was correlated with the onset of mitotic arrest in these cells, which have implications for cell cycle regulation. [ABSTRACT FROM AUTHOR]

Background Lung cancer remains the most common cause of cancer-related death, with high rates of recurrence and poor outcomes. An abnormally high expression of activating transcription factor 3 ( ATF3) in various cancers suggests an oncogenic role; however, its function in lung cancer is largely unknown. Methods Sixty-four pairs of lung cancer tissues were collected for ATF3 expression analysis by quantitative real-time PCR, immunoblotting, and immunohistochemistry staining. Correlations between ATF3 expression with clinicopathological features and overall survival were analyzed. ATF3 expression in a panel of lung cancer cell lines together with normal bronchial epithelial Beas-2 B cells was also determined. Human H1299 and A549 cells were used for ATF3 knockdown and/or overexpression assays. Alterations in cell proliferation, cell cycle attribution, migration, and invasion were all assessed in vitro. Results Increased ATF3 messenger RNA and protein expression were observed in lung cancer tissues/cells compared with normal tissues/cells. High tumorous ATF3 expression was significantly correlated with positive advanced tumor grade, lymph node metastasis, and shorter overall survival. Experimentally, we found that RNA interference mediated knockdown of ATF3 significantly inhibited the cell proliferation, cell cycle progression, migration, and invasion capacities of lung cancer cells in vitro, whereas forced expression of ATF3 did the opposite. Conclusion Upregulation of ATF3 in lung cancer promotes cell proliferation, migration, and invasion, and may represent a novel therapeutic target for lung cancer. [ABSTRACT FROM AUTHOR]

Fluorescence in situ hybridization (FISH) with centromeric probes is a method used to detect chromosomal instability (CIN), a hallmark of most cancers. However, no studies thus far have investigated the relationship between centromeric FISH signals and the cell cycle in cancer cells. In this study, the chromosome content in each cell cycle phase was evaluated with respect to the number of centromeric FISH signals in two breast cancer cell lines and eight surgically resected breast cancer specimens using image cytometry. Variations in chromosome number were detected at each phase of the cell cycle but were not associated with proliferative capacity in the cell lines. Furthermore, the chromosome doubling frequency differed in each cell line and clinical specimen. These results reveal two aspects of centromeric FISH signal variation in breast cancers that exhibit CIN, and suggest that chromosome doubling is a remarkable occurrence that may increase the heterogeneity of tumors. © 2014 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases (CDKs) generally regulate cell proliferation in dividing cells, including neural progenitors. In contrast, an unconventional CDK, Cdk5, is predominantly activated in post-mitotic cells, and involved in various cellular events, such as microtubule and actin cytoskeletal organization, cell-cell and cell-extracellular matrix adhesions, and membrane trafficking. Interestingly, recent studies have indicated that Cdk5 is associated with several cell cycle-related proteins, Cyclin-E and p27kip1. Taking advantage of multiple functionality, Cdk5 plays important roles in neuronal migration, layer formation, axon elongation and dendrite arborization in many regions of the developing brain, including cerebral cortex and cerebellum. Cdk5 is also required for neurogenesis at least in the cerebral cortex. Furthermore, Cdk5 is reported to control neurotransmitter release at presynaptic sites, endocytosis of the NMDA receptor at postsynaptic sites and dendritic spine remodeling, and thereby regulate synaptic plasticity and memory formation and extinction. In addition to these physiological roles in brain development and function, Cdk5 is associated with many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, I will introduce the physiological and pathological roles of Cdk5 in mammalian brains from the viewpoint of not only in vivo phenotypes but also its molecular and cellular functions. [ABSTRACT FROM AUTHOR]

In developing brains, neural progenitors exhibit cell cycle-dependent nuclear movement within the ventricular zone [interkinetic nuclear migration ( INM)] and actively proliferate to produce daughter progenitors and/or neurons, whereas newly generated neurons exit from the cell cycle and begin pial surface-directed migration and maturation. Dysregulation of the balance between the proliferation and the cell cycle exit in neural progenitors is one of the major causes of microcephaly (small brain). Recent studies indicate that cell cycle machinery influences not only the proliferation but also INM in neural progenitors. Furthermore, several cell cycle-related proteins, including p27kip1, p57kip2, Cdk5, and Rb, regulate the migration of neurons in the postmitotic state, suggesting that the growth arrest confers dual functions on cell cycle regulators. Consistently, several types of microcephaly occur in conjunction with neuronal migration disorders, such as periventricular heterotopia and lissencephaly. However, cell cycle re-entry by disturbance of growth arrest in mature neurons is thought to trigger neuronal cell death in Alzheimer's disease. In this review, we introduce the cell cycle protein-mediated regulation of two types of nuclear movement, INM and neuronal migration, during cerebral cortical development, and discuss the roles of growth arrest in cortical development and neurological disorders. [ABSTRACT FROM AUTHOR]