Disease relevance of Cell Cycle

• With this in mind, we performed DNA flow-cytometric measurements of ploidy and the fraction of cells in the synthesis phase of the cell cycle (S-phase fraction) on 395 specimens of node-negative breast cancer from our bank of frozen tumors, using the aliquots of pulverized frozen tissue from steroid-receptor assays [1].
• Here we show that the tyrosine kinase activity of nuclear c-Abl is regulated in the cell cycle through a specific interaction with the retinoblastoma protein (RB) [2].
• The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer [3].
• Introduction of the RB gene into SAOS-2 osteosarcoma cells, which lack functional pRb, prevents cell cycle progression [4].
• In contrast, mice expressing a mutant Cdk4 that cannot bind the cell-cycle inhibitor P16INK4a display pancreatic hyperplasia due to abnormal proliferation of beta-islet cells [5].

Psychiatry related information on Cell Cycle

• The role of these proteins in human disease coupled with biochemical evidence suggests that CBP and p300 are tumor suppressor proteins essential in cell-cycle control, cellular differentiation and human development [6].
• Recent studies in plants indicate that MAPK cascades are vital to fundamental physiological functions involved in hormonal responses, cell cycle regulation, abiotic stress signaling, and defense mechanisms [7].
• The cell cycle Cdc25A tyrosine phosphatase is activated in degenerating postmitotic neurons in Alzheimer's disease [8].
• The addition of 2-ME to the culture medium shifted the cell cycle kinetics toward and earlier peak response time (day 2), and significant differences among groups were seen only under suboptimal conditions [9].
• Neuronal changes supporting alterations in cell cycle control in the etiology of Alzheimer disease include the ectopic expression of markers of the cell cycle, organelle kinesis and cytoskeletal alterations including tau phosphorylation [10].

High impact information on Cell Cycle

• Tax exerts (a) trans-activation and -repression of transcription of different sets of cellular genes through binding to groups of transcription factors and coactivators, (b) dysregulation of cell cycle through binding to inhibitors of CDK4/6, and (c) inhibition of some tumor suppressor proteins [11].
• Finally, we present evidence demonstrating that B cell activation via TI stimuli does not play merely a permissive role in allowing for cell cycle entry and enhanced responsiveness to other stimuli [12].
• For example, if tumors are preferential glutamine utilizers, then TPN-enriched solutions might be employed to increase the number of cells in a phase of mitosis that makes them more susceptible to attack by cell-cycle specific chemotherapeutic agents [13].
• Mechanisms that control timing of cell cycle and developmental events include transcriptional cascades, regulated phosphorylation and proteolysis of signal transduction proteins, transient genetic asymmetry, and intercellular communication [14].
• Finally, PP1 promotes the exit from mitosis and maintains cells in the G1 or G2 phases of the cell cycle [15].

Chemical compound and disease context of Cell Cycle

• By comparison, the promoter of the herpes simplex virus (HSV) thymidine kinase gene is serum-stimulated but not cell-cycle regulated [16].
• These compounds also significantly inhibit estrogen-stimulated cell proliferation, markedly reduce tumor mass in nude mice bearing human MCF-7 breast cancer xenografts, and interfere with cell-cycle and apoptosis regulatory gene expression [17].
• The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, involved in de novo cholesterol synthesis and cell-cycle progression, was identified as a potential mediator of the growth inhibitory effects of retinoic acid on human neuroblastoma [18].
• To further study the mechanism of growth inhibition, we have purified lymphoma cells in G1 by centrifugal elutriation, or enriched WEHI-231 cells at the G1/S interface by treatment with hydroxyurea, and followed their progression through the cell cycle in the presence or absence of anti-mu [19].
• During the repair phase of transient renal ischemia, these cells entered the cell cycle and the BrdU signal quickly disappeared from the papilla, despite the absence of apoptosis in this part of the kidney [20].

Biological context of Cell Cycle

• The importance of p53 in carcinogenesis stems from its central role in inducing cell cycle arrest or apoptosis in response to cellular stresses [21].
• Ordering S phase and M phase in the cell cycle [22].
• The 70 kDa ribosomol S6 kinase (pp70S6k) plays an important role in the progression of cells through G1 phase of the cell cycle [23].
• BRCA1 immunostaining reveals discrete, nuclear foci during S phase of the cell cycle [24].
• These findings suggest that while certain members of the E2F family may positively regulate cell cycle progression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation [25].

Anatomical context of Cell Cycle

• salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines [26].
• gamma-Irradiation of human diploid fibroblasts in the G1 interval caused arrest of the cell cycle prior to S phase [27].
• These data indicate that L-CA is required for T cells to enter into cell cycle in response to antigen [28].
• Catabolism of thymidine during the lymphocyte cell cycle [29].
• Hepatocytes from Timp3(-/-) mice completed the cell cycle but then underwent cell death owing to sustained activation of TNF [30].

Associations of Cell Cycle with chemical compounds

• As in the case of cell cycle control, protein serine/threonine phosphatase plays a central role in the reentry of quiescent cells into the cycle [31].
• Analysis of extracts of thymidine-blocked cells confirms that the complexes are cell cycle regulated [32].
• These observations have been interpreted to indicate that estradiol and FSH can each alter the length of the specific phases of the cell cycle [33].
• Overexpression of dominant negative c-abl disrupts cell cycle control and enhances transformation by tyrosine kinases, G proteins, and transcription factor oncogenes [34].
• Upon regulation of expression of GPA1 by the galactose-inducible GAL1 promoter, the loss of GPA1 function was found to lead to cell-cycle arrest at the late G1 phase [35].

Gene context of Cell Cycle

• Cotransfection experiments indicate that CIP1 and SV40 T antigen function in a mutually antagonistic manner to control cell cycle progression [36].
• TGF beta inhibition of Cdk4 synthesis is linked to cell cycle arrest [37].
• The c-Myc and E2F transcription factors are among the most potent regulators of cell cycle progression in higher eukaryotes [38].
• Economical reutilization of coding sequences in this manner is practically without precedent in mammalian genomes, and the unitary inheritance of p16INK4a and p19ARF may underlie their dual requirement in cell cycle control [39].
• Thus, identification of factors that interfere with and/or control the function of the RB protein is critical for understanding both cell-cycle control and oncogenesis [40].

Analytical, diagnostic and therapeutic context of Cell Cycle

• Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase) [41].
• A model of cell cycle control: effects of thymidine on synchronous cell cultures [42].
• Importantly, antibody microinjection experiments suggest a role for BRCA2/BRAF35 complex in modulation of cell cycle progression [43].
• Here we have investigated the significance of this phenomenon by molecular cloning of p21 and in vitro reconstitution of the quaternary cell-cycle kinase complexes [44].
• The cell-cycle element (CCE) required for H4 histone activation is a sequence of 11 base pairs that binds a protein factor in electrophoretic mobility shift assays that has been designated histone nuclear factor M (HiNF-M) [45].

References