Disease relevance of G1 Phase

• Wild-type S49 lymphoma cells respond to cyclic adenosine 3', 5'-monophosphate (cAMP) by inducing cAMP phosphodiesterase, halting growth in the G1 phase of the cell cycle and subsequently dying [1].
• Null mutations cause hyperplasia of all tissues. cul-1 is required for developmentally programmed transitions from the G1 phase of the cell cycle to the GO phase or the apoptotic pathway [2].
• The product (pRb) of the retinoblastoma gene (RB-1) prevents S-phase entry during the cell cycle, and inactivation of this growth-suppressive function is presumed to result from pRb hyperphosphorylation during late G1 phase [3].
• After 2 days of ERBB2 suppression, breast cancer cells showed an accumulation in the G1 phase of the cell cycle [4].
• This assay was applied to human A2780 ovarian carcinoma cells treated with cisplatin at the beginning of G1 phase [5].

Psychiatry related information on G1 Phase

• Presenilin overexpression arrests cells in the G1 phase of the cell cycle. Arrest potentiated by the Alzheimer's disease PS2(N141I)mutant [6].

High impact information on G1 Phase

• Whi5 associates with G1-specific promoters via SBF during early G1 phase, then dissociates coincident with transcriptional activation [7].
• The G1 phase of the cell cycle was prolonged, but there was no effect on the utilization of either the c-Myc or beta-globin cellular origins of replication [8].
• We present evidence that Rb forms a repressor containing histone deacetylase (HDAC) and the hSWI/SNF nucleosome remodeling complex, which inhibits transcription of genes for cyclins E and A and arrests cells in the G1 phase of the cell cycle [9].
• In synchronized HeLa cells, geminin is absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase-anaphase transition [10].
• Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation [11].

Chemical compound and disease context of G1 Phase

• Hexamethylenebisacetamide (HMBA), a potent inducer of differentiation of transformed cells such as murine erythroleukemia cells, causes a prolongation of the G1 phase of the cell cycle during which commitment to terminal differentiation is first detected [12].
• In order to elucidate the mechanisms by which estrogens and antiestrogens modulate the growth of breast cancer cells, we have characterized the changes induced by estradiol that occur during the G1 phase of the cell cycle of MCF-7 human mammary carcinoma cells [13].
• We have previously shown that cultured mesangial cells exposed to high glucose are arrested in the G1-phase of the cell cycle and undergo cellular hypertrophy [14].
• In cells expressing simian virus 40 (SV40) large T antigen, by infection with SV40 in the previous generation, the prolongation of G1 phase in the presence of cycloheximide was suppressed [15].
• In studies reported here, we compared the expression of the genes that code for the M1 and M2 subunits of ribonucleotide reductase in S49 cells, which are arrested in G1 phase by agents that increase cyclic AMP, with those from CEM human T lymphoma cells that are unaffected by exposure to dibutyryl cyclic AMP [16].

Biological context of G1 Phase

• Results showed that estrogen stimulated the recovery of growth from G0 arrest induced by nutrient limitation or ts mutation of cdc35 (adenylate cyclase) in the early G1 phase, and inhibited entry into the resting G0 phase by increasing the intracellular cAMP level [17].
• Inhibition of cyclin A synthesis or activity through microinjection of plasmids encoding antisense cyclin A cDNA or affinity-purified anti-cyclin A antibodies during G1 phase was shown to abolish the nuclear staining for cyclin A in plasmid-injected cells, and both procedures led to inhibition of DNA synthesis [18].
• This activation results in either arrest of the cell cycle in phase G1 or apoptotic cell death, both of which are dependent on the kinase activity of c-Abl. p73, a member of the p53 family of tumour-suppressor proteins, can also induce apoptosis [19].
• The weak CPD sites in Sic1 establish a phosphorylation threshold that delays degradation in vivo, and thereby establishes a minimal G1 phase period needed to ensure proper DNA replication [20].
• The F-box protein Cdc4 captures phosphorylated forms of the cyclin-dependent kinase inhibitor Sic1 for ubiquitination in late G1 phase, an event necessary for the onset of DNA replication [20].

Anatomical context of G1 Phase

• CLN3 is not required in daughter cells, but is crucial for mother cells, in which the G1 phase is much longer in the absence of this cyclin [21].
• TGF-beta 1 is demonstrated to inhibit skin keratinocyte proliferation when added during the G1 phase of the cell cycle [22].
• Although most cells were in the quiescent phase of the cycle, a significant increase was seen in the percentage of cells in the first stage of the proliferative cycle (G1 phase) when 21 samples of cerebrospinal fluid from 17 patients with MS were compared with samples from 21 controls (P < 0.001) [23].
• This cyclin E/E2F complex was seen in a variety of human cell lines from various tissues, but its appearance was detected primarily during the G1 phase of the cell cycle [24].
• In rat arterial smooth muscle cells overexpressing MKP-1, growth was arrested in the G1 phase and entry into the S phase was blocked [25].

Associations of G1 Phase with chemical compounds

• The effects of beta-estradiol (estrogen; a minor component of yeast cells) on S. cerevisiae cells in the G0 and G1 phases were examined [17].
• Assessment of cultures synchronized by double thymidine block and cells fractionated by centrifugation of a Ficoll gradient indicated that the RBL-1 cells acquire receptors in the G1 phase of the cell cycle [26].
• DMSO resulted in an early, transient (18-24 hr) accumulation of cells in G1 phase followed by a later (5 day), irreversible accumulation of G1 cells [27].
• A continuous iv infusion of [14C]N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour) [28].
• This subpopulation, termed "Q-cells," contained markedly reduced RNA and protein levels and had a cell cycle distribution with a predominance of cells in G1 phase, which was nearly identical to that found in fully differentiated dimethyl sulfoxide (CAS:67-68-5; methyl sulfoxide)-induced FL cultures [29].

Gene context of G1 Phase

• Using strains where CLN1 was expressed conditionally, the essential function of Cln proteins was found to be limited to the G1 phase [30].
• Cyclin D-dependent kinases phosphorylate Rb to control its activity and they are, in turn, specifically inhibited by the Ink4 family of cyclin-dependent kinase inhibitors (CDKIs) which cause arrest at the G1 phase of the cell cycle [31].
• But here we show that G1 cyclins are unstable in G1 phase, and that Clb-Cdc28 activity is not needed fgr G1 cyclin turnover [32].
• Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G1 phase to the S phase of the cell cycle [33].
• Cyclin D1 is a key regulator of the G1 phase of the cell cycle [34].

Analytical, diagnostic and therapeutic context of G1 Phase

• Furthermore, there were discrete G1 phase (prereplicative stage in the cell cycle) abnormalities including absence of STAT3 (signal transducer and activator of transcription protein 3) activation and depressed AP-1, Myc, and cyclin D1 expression [35].
• Flow cytometry of mithramycin-stained cells reveals that cells accumulate in G1 phase, with a concomitant depletion of S- and G2-M-phase cells with tamoxifen [36].
• Previously, we have shown that both T and B lymphocytes from chronically nicotine-treated (NT) animals exhibit tolerance to activation by Ags (ligation of Ag receptors), as indicated by their decreased ability to mobilize intracellular calcium and, at least in T cells, arrest of cells in the G0/G1 phase of the cell cycle [37].
• We have examined the possibility that FGF-1 employs c-Src or Src-like kinases as signaling intermediates during the mid and late G1 phase of the NIH 3T3 cell cycle using immunoprecipitation and immunoblot analysis [38].
• Cell cycle analysis showed an increased accumulation of cells in the G0/G1 phase after treatment with NS-398, but not with COX siRNAs [39].

References