scholarly journals Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.

1996 ◽  
Vol 183 (5) ◽  
pp. 2219-2226 ◽  
Author(s):  
S Mazel ◽  
D Burtrum ◽  
H T Petrie
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Division ◽  
Programmed Cell Death ◽  
Cell Cycle Progression ◽  
Control Point ◽  
Cell Division Cycle ◽  
Cell Cycle Distribution ◽  
Cycle Progression ◽  
Critical Control Point

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point.

Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water

1997 ◽  
Vol 16 (9) ◽  
pp. 485-494 ◽  
Author(s):  
Aristo Vojdani ◽  
Eli Mordechai ◽  
Nachman Brautbar
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Level ◽  
Control Group ◽  
Pyrrolidine Dithiocarbamate ◽  
Cycle Progression ◽  
Tertiary Butyl

1 In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce pro grammed cell death. 2 Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene- 5 contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3 Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4 When apoptotic lymphocytes from exposed indivi duals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 ± 1.8 and 12.1 ± 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals ( P<0.0001, Mann-Whitney U-Test). MTBE and ben- a zene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumu lated at the S-G2/M boundaries. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kB). NF-kB was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kB activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kB activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death.

scholarly journals Mitogen-independent cell cycle progression in B lymphocytes

2019 ◽  
Author(s):  
Amit Singh ◽  
Matthew H. Spitzer ◽  
Jaimy P. Joy ◽  
Mary Kaileh ◽  
Xiang Qiu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Division ◽  
B Lymphocytes ◽  
Cell Cycle Progression ◽  
Adaptive Immune System ◽  
G1 Phase ◽  
Cycle Progression ◽  
Extensive Cell Death ◽  
Extensive Cell

AbstractThe canonical view of the cell cycle posits that G1 progression signals are essential after each mitosis to enter S phase. A subset of tumor cells bypass this requirement and progress to the next cell division in the absence of continued signaling. B and T lymphocytes of the adaptive immune system undergo a proliferative burst, termed clonal expansion, to generate pools of antigen specific cells for effective immunity. There is evidence that rules for lymphocyte cell division digress from the canonical model. Here we show that B lymphocytes sustain several rounds of mitogen-independent cell division following the first mitosis. Such division is driven by unique characteristics of the post mitotic G1 phase and limited by extensive cell death that can be circumvented by appropriate anti-apoptotic signals. An essential component for continued cell division is Birc5 (survivin), a protein associated with chromosome segregation in G2/M. Our observation provides direct evidence for Pardee’s hypothesis that retention of features of G2M in post-mitotic cells could trigger further cell cycle progression. The partially active G1 phase and propensity for apoptosis that is inherited after each division may permit rapid burst of proliferation and cell death that are hallmarks of immune responses.

Modelling the controls of the eukaryotic cell cycle

2003 ◽  
Vol 31 (6) ◽  
pp. 1526-1529 ◽  
Author(s):  
B. Novák ◽  
J.J. Tyson
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Mathematical Modelling ◽  
Dynamic Characteristics ◽  
Cell Cycle Progression ◽  
Eukaryotic Cell ◽  
Cell Division Cycle ◽  
Comprehensive Model ◽  
Cycle Progression

The eukaryotic cell-division cycle is regulated by three modules that control G1/S, G2/M and meta/anaphase transitions. By using mathematical modelling, we show the dynamic characteristics of these individual modules and we also assemble them together into a comprehensive model of the eukaryotic cell-division cycle. With this comprehensive model, we also discuss the mechanisms by which different checkpoint pathways stabilize different cell-cycle states and inhibit the transitions that drive cell-cycle progression.

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

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