Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “G1 Phase”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1993

ADP-ribosylation of the rhoA gene product by botulinum C3 exoenzyme causes Swiss 3T3 cells to accumulate in the G1 phase of the cell cycle.

Using botulinum C3 exoenzyme, which specifically ADP-ribosylates the rho gene products (rho proteins), we examined the role of these proteins in cell cycle progression in Swiss 3T3 cells. Incubation of cell lysates with C3 exoenzyme revealed a single [32P]ADP-ribosylated protein with an M(r) of 23K. This protein was identified as rhoA protein by isoelectric focusing and peptide mapping. When C3 exoenzyme was added to the culture, it ADP-ribosylated the substrate protein in the cells and reduced their growth rate and saturation density. The reduction was dependent on the amount of C3 exoenzyme and on the extent of ADP-ribosylation of the rho protein in the cells. Flow cytometric analysis of logarithmically growing cells showed that the enzyme treatment concentration-dependently accumulated the cells in the G1 phase of the cell cycle. When G1-enriched cells were treated with C3 exoenzyme and cell cycle progression initiated by the addition of serum was monitored, inhibition of G1-S transition was clearly observed. These results suggest that the rhoA gene product plays a critical role in G1-S progression in cultured Swiss 3T3 cells and that the ADP-ribosylation abolishes this activity and causes the cells to accumulate in G1 phase.

3T3 Cells↗
PubMed1998

Evidence for introduction of a variable G1 phase at the midblastula transition during early development in axolotl.

After fertilization in axolotl, the synchronous cell cleavages are triphasic (S, G2 and M phases). Midblastula transition (MBT) begins at the ninth cleavage and is the consequence of lengthening of cell cycles. By spectrofluorometry and incorporation of 3H thymidine into the nuclear DNA followed by autoradiography on individual cells, the time at which a G1 phase appears during early development was investigated. The present results show that the G1 phase was introduced for the first time at MBT and its duration was variable from one blastomere to another. This variability could account for lengthening of cell cycles and be required for zygotic transcriptions necessary for DNA replication. From this point of view, axolotl represents an interesting alternative amphibian model to identify regulators involved in the G1-S transition at MBT during early development.

Ambystoma↗
PubMed1991

The anticonvulsant valproate teratogen restricts the glial cell cycle at a defined point in the mid-G1 phase.

Direct cell counting and extent of [3H]thymidine incorporation demonstrated valproate to inhibit C6 glioma proliferation rate in a dose-dependent manner with a 1 mM concentration achieving 50% inhibition. The antiproliferative effect was reversible and could not be attributed to cytotoxicity at the valproate concentrations employed. The site of valproate action within the cell cycle was determined to be in the G1 phase, at a point 6-6.5 h prior to S phase, by estimating the time to increased [3H]thymidine incorporation following release from a 70% proliferative arrest. Synchronised cells obtained by a mitotic selection procedure required 11-12 h to enter S phase and demonstrated the valproate restriction point to be 5 h into the G1 phase of the C6 cell cycle. Exposure of valproate to the part of the G1 period which follows the restriction point was without effect on cell entry into S phase.

Animals↗
PubMed1999

NA22598, a novel antitumor compound, reduces cyclin D1 levels, arrests cell cycle at G1 phase, and inhibits anchorage-independent growth of human tumor cells.

NA22598, a novel antitumor compound isolated from a microbial cultured broth, inhibited the growth of human colon cancer DLD-1 cells in suspension cultures (anchorage-independent growth) severalfold more strongly than in substratum-attached monolayer cultures. It arrested the cell cycle progression at early G1 phase under both these culture conditions. Rb phosphorylation, cyclin D1 expression, and cdk2 activation in G1 progression were all inhibited by NA22598, but the amounts of cdk2 and p27 were not affected. Among these effects the inhibition of cyclin D1 expression was most prominent, and NA22598 was found to inhibit the synthesis of cyclin D1 without affecting mRNA expression or protein degradation. p27 binding to cdk2 was more markedly increased in suspension cultures than in attached cultures by NA22598, but the compound had no effect on total p27. Apparently, the decrease of cyclin D1 induced redistribution of p27 from the cyclin D1/cdk4 to the cyclin E/cdk2 complexes during G1 phase in the suspension cultures. Because p27 is upregulated during suspension culture, a greater amount of it was associated with cyclin E/cdk2, thus producing greater growth inhibition. An agent, like NA22598, which induces the downregulation of cyclin D1 might offer a new anticancer strategy.

Antineoplastic Agents↗
PubMed1987

125IdUrd-induced chromosome fragments, assayed by premature chromosome condensation, and DNA double-strand breaks have similar repair kinetics in G1-phase CHO-cells.

The effect of 125I-decay on cell lethality, and induction of chromosome and DNA damage, was studied in synchronous non-cycling, G1-phase CHO-cells. For this purpose a population of mitotic cells was allowed to divide and progress through S-phase in the presence of 125IdUrd. Cells were subsequently transferred to conditioned medium (C-med) obtained from plateau-phase cultures that allowed cells to divide and accumulate in G1-phase in a non-cycling state. To accumulate 125I-induced damage, cells were kept frozen at -80 degrees C. Freezing was carried out using a new method that optimally preserves cell integrity. After various times of cold storage, cells were thawed and assayed for survival, DNA and chromosome damage, either immediately or after various times in C-med. Neutral filter elution was used to assay repair of DNA double-strand breaks (dsbs), and premature chromosome condensation was used to assay repair of chromosome fragments and induction of ring chromosomes. The results indicate very little repair at the cell survival level (repair of PLD). At the DNA level an efficient repair of DNA dsbs was observed, with kinetics similar to those observed after exposure to X-rays. At the chromosome level a fast repair of prematurely condensed chromosome fragment was observed, with a concomitant increase in the number of ring chromosomes induced. The repair kinetics of chromosome fragments and DNA dsbs were very similar, suggesting that DNA dsbs may underlie chromosome fragmentation.

Animals↗
PubMed1975

Instability of the duration of G1 phase of Yoshida sarcoma and ascites hepatomas.

The durations and coefficients of variance of G1, S and G2 phase were obtained for 8 cell lines of ascites tumours originated from hepatomas in rats, and these were compared. Although changes in the durations of S and G2 phases were small, the duration of G1 phase increased with the cell cycle time. The coefficient of variance of G1 phase was larger than that of S and G2 phases, most remarkedly at short cycle time. It was concluded that the G1 phase is the most unstable as well as the most variable in its duration.

Animals↗
PubMed1995

Fusobacterium nucleatum inhibits human T-cell activation by arresting cells in the mid-G1 phase of the cell cycle.

Fusobacterium nucleatum has been implicated in the pathogenesis of several diseases, including urinary tract infections, bacteremia, pericarditis, otitis media, and disorders of the oral cavity such as pulpal infections, alveolar bone abscesses, and periodontal disease. We have previously demonstrated that sonic extracts of F. nucleatum FDC 364 were capable of inhibiting human T-cell responses to mitogens and antigens. In this study, we have further characterized this immunosuppressive protein (FIP) and initiated experiments to determine its mode of action. The purified FIP has an apparent molecular mass of 90 to 100 kDa; sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that the FIP is actually composed of two subunits with molecular masses of 48 and 44 kDa. Purified FIP retained its biological activity and was capable of inhibiting mitogen-induced proliferation of human T cells. Inhibition was dose dependent, and the FIP exhibited a specific activity approximately 250-fold greater than that of the crude extract. Cell cycle analysis indicates that FIP-treated cells were prevented from exiting the G0/G1 phase of the cell cycle. However, FIP did not alter the expression of activation markers (CD69, CD25, and CD71) or interleukin-2 secretion. The latter observations suggest that the T cells did indeed become activated and had entered the G1 phase of the cell cycle. Analysis of the expression of cyclins indicates that the phase of the cell cycle that is FIP sensitive resides somewhere beyond the restriction point of cyclin D2 (early to mid-G1) but prior to that of cyclins D3 and E (mid- to late G1). Finally, analysis of the expression of the proliferating cell nuclear antigen indicates that this is the earliest detectable defect in T cells exposed to FIP. We propose that if a block in the G1 phase of the cell cycle occurs in vivo in lymphocytes, it may result in a state of local and/or systemic immunosuppression. These suppressive effects could alter the nature and consequences of host-parasite interactions, thereby enhancing the pathogenicity of F. nucleatum itself or that of some other opportunistic organisms.

Bacterial Proteins↗
PubMed2004

Insulin-like growth factor-I accelerates the cell cycle by decreasing G1 phase length and increases cell cycle reentry in the embryonic cerebral cortex.

Neurogenesis in the developing cerebral cortex of mice occurs in the dorsal telencephalon between embryonic day 11 (E11) and E17, during which time the majority of cortical projection neurons and some glia are produced from proliferating neuroepithelial cells in the ventricular zone. The number of cells produced by this process is governed by several factors, including cell cycle kinetics and the proportion of daughter cells exiting the cell cycle after a given round of cell division. The in vivo effects of IGF-I on cell cycle kinetics were investigated in nestin/IGF-I transgenic (Tg) embryos, in which IGF-I is overexpressed in the cerebral cortex and dorsal telencephalon. These Tg mice have been shown to exhibit increased cell number in the cortical plate by E16 and increased numbers of neurons and glia in the cerebral cortex during postnatal development. Cumulative S phase labeling with 5-bromo-2'-deoxyuridine revealed a decrease in total cell cycle length (TC) in Tg embryos on E14. This decrease in TC was found to result entirely from a reduction in the length of the G1 phase of the cell cycle from 10.66 to 8.81 hr, with no significant changes in the lengths of the S, G2, and M phases. Additionally, the proportion of daughter cells reentering the cell cycle was significantly increased by 15% in Tg embryos on E14-E15 compared with littermate controls. These data demonstrate that IGF-I regulates progenitor cell division in the ventricular zone by reducing G1 phase length and decreasing TC but increases cell cycle reentry.

Animals↗
PubMed1998

The cyclin-dependent kinase inhibitors olomoucine and roscovitine arrest human fibroblasts in G1 phase by specific inhibition of CDK2 kinase activity.

The specificity and the temporal location of cell cycle arrest induced by the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine were investigated in normal human fibroblasts. Effects on the cell cycle were compared with those induced by the kinase inhibitor staurosporine, which arrests normal cells in early G1 phase by acting upstream of CDK2. Consistent with their in vitro activity, olomoucine and roscovitine, but not the related compound iso-olomoucine, induced a dose-dependent arrest in G1 phase. Following removal of CDK inhibitors, cells resumed cycle progression entering S phase with a kinetics faster than staurosporine-treated samples. Cellular levels of PCNA, cyclin D1, and cyclin E were not affected by the CDK inhibitors. In contrast, staurosporine significantly reduced the levels of these proteins, as determined by immunocytometry and Western blot analysis. Cyclin A was detectable only in some cells remaining in the G2 + M compartment of samples treated with CDK inhibitors, but not in samples treated with staurosporine. Significant reduction in the hyperphosphorylated forms of retinoblastoma protein was found in samples treated with CDK inhibitors, while only hypophosphorylated forms were observed in staurosporine-treated samples. Concomitantly, CDK2, but not CDK4, activity immunoprecipitated from cells treated with olomoucine or roscovitine was markedly inhibited. These results suggest that in normal cells, CDK2 kinase activity is the specific target of olomoucine and roscovitine.

CDC2-CDC28 Kinases↗
PubMed1982

S-100 protein synthesis in cultured glioma cell is G1-phase of cell cycle dependent.

The kinetics of S-100 protein synthesis was studied in synchronized cultured glioma (C6) cells. The peak of the synthesis was detected at G1-phase of the cell cycle and apparently was not population density-dependent, since sparsely cultured G1-phase cells synthesized the same proportion of the protein per cell as that of confluent cultures, whereas the total cellular protein synthesis was found steadily increasing throughout the intermitotic phases.

Animals↗
PubMed2000

Integrating the MAP kinase signal into the G1 phase cell cycle machinery.

Growth factors and the extracellular matrix provide the environmental cues that control the proliferation of most cell types. The binding of growth factors and matrix proteins to receptor tyrosine kinases and integrins, respectively, regulates several cytoplasmic signal transduction cascades, among which activation of the mitogen-activated protein kinase cascade, ras --> Raf --> MEK --> ERK, is perhaps the best characterized. Curiously, ERK activation has been associated with both stimulation and inhibition of cell proliferation. In this review, we summarize recent studies that connect ERK signaling to G1 phase cell cycle control and suggest that the cellular response to an ERK signal depends on both ERK signal intensity and duration. We also discuss studies showing that receptor tyrosine kinases and integrins differentially regulate the ERK signal in G1 phase.

Animals↗
PubMed1992

Measurement of efflux from G1-phase in a growth factor dependent cell line.

In order to test a mathematical model of G1/S-phase transition, the proliferative response of the murine myeloid interleukin 3 (IL-3) dependent cell line NFS-78 to graded reduction of IL-3 levels was measured. Exponentially growing cells were exposed to bromodeoxyuridine (BUdR), which replaces thymidine (TdR) in the DNA double strands during DNA synthesis. After incubation periods ranging from 3 to 36 h the cells were fixed and stained with a fluorescence dye mixture of Hoechst 33258 and ethidium bromide (EB) and subsequently analyzed in a two-parametrical flow cytometer. The BUdR-quenched TdR-specific Hoechst 33258 fluorescence of each cell provides information on the cell cycle location at the start of incubation and on whether or not a cell has divided. The DNA-specific EB fluorescence provides information on the actual cell cycle location at the end of the incubation period. From the 2-dimensional fluorescence distributions the efflux from G1-phase was calculated. Upon IL-3 reduction the cells showed accumulation in the G1-phase along with a reduction in the progression rate through the other phases of the cell cycle. By staining with the vital dye Hoechst 33342 as well as with propidium iodide (PI) it was further possible to show that cell death after IL-3 withdrawal occurred in all phases of the cell cycle.

Animals↗
PubMed1998

Effect of transient cyclic AMP elevation on DNA synthesis in rat hepatocytes at G1 phase.

Maintaining high levels of intracellular cyclic AMP (cAMP) is known to inhibit the growth of various proliferating cells including hepatocytes. We show here that transient (30 min) elevations of cAMP induced by addition of 8-bromo-cAMP (1 mmol/L) to rat hepatocytes in primary culture at three time points (12 h, 16 h and 20 h) after seeding stimulated DNA synthesis. Sustained levels of cAMP stimulated DNA synthesis to a lesser degree at a lower concentration (1 mumol/L), but inhibited it at concentrations higher than 100 mumol/L. We also determined cyclin-dependent kinase 2 (cdk2) activity in the hepatocytes during this incubation period. The transient addition of 8-bromo-cAMP at the late G1 phase increased cdk2 activity. This suggests that transient cAMP elevation in hepatocytes at the late G1 phase has a growth stimulation effect. Up-regulation of cdk2 activity may have a role in this process.

Animals↗
PubMed1998

Stimulation of heparan sulfate proteoglycan synthesis and secretion during G1 phase induced by growth factors and PMA.

Fetal calf serum (FCS) and PMA (phorbol 12-myristate-13-acetate) specifically stimulate the synthesis of heparan sulfate proteoglycan in endothelial cells. Staurosporine and n-butanol, kinase inhibitors, abolish the PMA effect. Forskolin and 8-bromo adenosine 3':5'-cyclic monophosphate, activators of, respectively, adenylate cyclase and protein kinase A cannot reproduce the PMA effect. The kinetics of cell entry into S phase of the endothelial cells was determined by DNA synthesis ([3H]-thymidine and Br-dU incorporation), and flow cytometry. The mitogenic effect of fetal calf serum is abolished by PMA. Also, PMA pre-treatment inhibits the enhanced synthesis of heparan sulfate proteoglycan after a second PMA exposure. Remarkably, the stimulation of heparan sulfate proteoglycan synthesis by fetal calf serum and PMA seems to be mainly restricted to G1 phase. Therefore fetal calf serum and PMA cause an enhanced synthesis of heparan sulfate proteoglycan, and PMA causes a cell cycle block at G1 phase.

Animals↗
PubMed1998

Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25-dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1 phase.

Drug resistance that occurs during cancer chemotherapy has been a major problem in controlling neoplastic progression. To study the cellular mechanisms of acquired drug resistance we developed 1,25-dihydroxyvitamin D3 (1,25D3)-resistant sublines of promyelocytic leukemia HL60 cells which have increased proliferation rates (Exp. Cell Res., 224, 312, 1996; Cancer Res., 50, 5513, 1996). We report here that the resistant sublines display varying degrees of shortening of the G1 phase as compared to the parental HL60-G cells. Protein levels of cyclins E, D1, D2 and D3 are elevated in these resistant cell lines, and cyclin D1 is especially high in 40AF cells, which has the shortest G1 length. The protein levels of cyclin-dependent kinase (Cdk)2, Cdk4 and Cdk6 are not altered in the resistant sublines. Both Cdk2 and Cdk6-associated kinase activites are increased in the resistant sublines, but not Cdk4 kinase activity. Protein levels of p27Kip1 are not consistently altered in the resistant sublines as compared to the parental HL60-G cells, but are reduced relative to HL60-G cells arrested by 96 h treatment with 1,25D3. Interestingly, the resistant cell lines constitutively express high levels of retinoblastoma protein (pRb), and pRb is highly phosphorylated, indicating that the G1 cyclin/Cdk complexes in the resistant cells are physiologically active. The results suggest that the increased activity of cyclin D/Cdk6, and perhaps cyclin E/Cdk2, lead to rapid hyperphosphorylation of pRb and consequently a shorter early G1 phase, and that in the resistant cells the increased ratio of cyclin E to p27Kip1 results in activation of Cdk2 and contributes to the abrogation of the 1,25D3-induced block to the S phase entry. Additionally, it is apparent that constitutively increased levels of pRb are compatible with increased rates of cell proliferation.

CDC2-CDC28 Kinases↗
PubMed1996

[Retardation of human drug-resistant HL-60 cell in G1 phase and induction of sensitive cell to apoptosis by cyclosporine A].

To further study the relationship between resistance to apoptosis and drug resistance in harringtonine-resistant HL-60 cells (HR20), cyclosporine A (CsA) 20, 10 micrograms.ml-1 was shown to induce the sensitive HL-60 cells to apoptosis, showing a typical DNA "ladder" band. But the same concentrations of CsA retarded the HR20 cells in G1 phase and could not induce the cells to apoptosis. The cellular daunorubicin accumulation increased when HR20 cells were treated with low concentration of CsA and the reversal of drug resistance by CsA was unrelated to the retardation of cell cycle progression. High phosphorylation of about 50 kDa protein occured when HR20 cells were treated with CsA 10 micrograms.ml-1. The results domonstrate that cyclosporine A retarded the harringtonine-resistant HL-60 cells in G1 phase but induced HL-60 cells to apoptosis, and the retardation was unrelated to drug resistance.

Antineoplastic Agents, Phytogenic↗
PubMed1987

A 63 kDa protein is secreted from BALB/c-3T3 cells entering the G1 phase from the G0 state.

A 63 kDa protein is detectable in the culture fluid of mouse BALB/c-3T3 cells traversing from the G0 state to the G1 phase, whereas it is undetectable in the culture fluid of quiescent or growing BALB/c-3T3 cells. Secretion of the protein is maximal at 10 h after serum addition. G0-specific ts mutant cells (rat tsJT60) also secrete the 63 kDa protein only when the quiescent cells are stimulated by serum addition at permissive temperature. These facts indicate that the 63 kDa protein is secreted only from cells traversing from the G0 state to the G1 phase.

Animals↗