scholarly journals Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1.

1996 ◽  
Vol 16 (6) ◽  
pp. 2830-2837 ◽  
Author(s):  
L J Oehlen ◽  
J D McKinney ◽  
F R Cross
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
G1 Phase ◽  
Protein Accumulation ◽  
Transcriptional Activation Domain ◽  
Cycle Arrest ◽  
Gal1 Promoter ◽  
Combinatorial Control ◽  
Cycle Dependent

The transcripts of many genes involved in Saccharomyces cerevisiae mating were found to fluctuate during the cell cycle. In the absence of a functional Ste12 transcription factor, both the levels and the cell cycle pattern of expression of these genes were affected. FUS1 and AGA1 levels, which are maximally expressed only in G1-phase cells, were strongly reduced in ste12- cells. The cell cycle transcription pattern for FAR1 was changed in ste12- cells: the gene was still significantly expressed in G2/M, but transcript levels were strongly reduced in G1 phase, resulting in a lack of Far1 protein accumulation. G2/M transcription of FAR1 was dependent on the transcription factor Mcm1, and expression of a gene with Mcm1 fused to a strong transcriptional activation domain resulted in increased levels of FAR1 transcription. The pattern of cell cycle-regulated transcription of FAR1 could involve combinatorial control of Ste12 and Mcm1. Forced G1 expression of FAR1 from the GAL1 promoter resorted the ability to arrest in response to pheromone in ste12-cells. This indicates that transcription of FAR1 in the G1 phase is essential for accumulation of the protein and for pheromone-induced cell cycle arrest.

scholarly journals Glucocorticoid receptor-mediated cell cycle arrest is achieved through distinct cell-specific transcriptional regulatory mechanisms.

1997 ◽  
Vol 17 (6) ◽  
pp. 3181-3193 ◽  
Author(s):  
I Rogatsky ◽  
J M Trowbridge ◽  
M J Garabedian
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Transcriptional Activation ◽  
Growth Arrest ◽  
Receptor Activation ◽  
Regulatory Mechanisms ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Cycle Arrest ◽  
U2os Cells

Glucocorticoids inhibit proliferation of many cell types, but the events leading from the activated glucocorticoid receptor (GR) to growth arrest are not understood. Ectopic expression and activation of GR in human osteosarcoma cell lines U2OS and SAOS2, which lack endogenous receptors, result in a G1 cell cycle arrest. GR activation in U2OS cells represses expression of the cyclin-dependent kinases (CDKs) CDK4 and CDK6 as well as their regulatory partner, cyclin D3, leading to hypophosphorylation of the retinoblastoma protein (Rb). We also demonstrate a ligand-dependent reduction in the expression of E2F-1 and c-Myc, transcription factors involved in the G1-to-S-phase transition. Mitogen-activated protein kinase, CDK2, cyclin E, and the CDK inhibitors (CDIs) p27 and p21 are unaffected by receptor activation in U2OS cells. The receptor's N-terminal transcriptional activation domain is not required for growth arrest in U2OS cells. In Rb-deficient SAOS2 cells, however, the expression of p27 and p21 is induced upon receptor activation. Remarkably, in SAOS2 cells that express a GR deletion derivative lacking the N-terminal transcriptional activation domain, induction of CDI expression is abolished and the cells fail to undergo ligand-dependent cell cycle arrest. Similarly, murine S49 lymphoma cells, which, like SAOS2 cells, lack Rb, require the N-terminal activation domain for growth arrest and induce CDI expression upon GR activation. These cell-type-specific differences in receptor domains and cellular targets linking GR activation to cell cycle machinery suggest two distinct regulatory mechanisms of GR-mediated cell cycle arrest: one involving transcriptional repression of G1 cyclins and CDKs and the other involving enhanced transcription of CDIs by the activated receptor.

scholarly journals FAR1 and the G1 phase specificity of cell cycle arrest by mating factor in Saccharomyces cerevisiae.

1995 ◽  
Vol 15 (5) ◽  
pp. 2509-2516 ◽  
Author(s):  
J D McKinney ◽  
F R Cross
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
G1 Phase ◽  
Cycle Arrest ◽  
Gal1 Promoter ◽  
G1 Phase Arrest ◽  
Terminal Amino ◽  
Cycle Regulation ◽  
Mating Factor

Significant accumulation of Far1p is restricted to the G1 phase of the Saccharomyces cerevisiae cell cycle. Here we demonstrate yeast cell cycle regulation of Far1p proteolysis. Deletions within the 50 N-terminal amino acids of Far1p increase stability and reduce cell cycle regulation of Far1p abundance. Whereas wild-type Far1p specifically and exclusively promotes G1 phase arrest in response to mating factor, stabilized Far1p promoted arrest both during and after G1. The loss of the G1 specificity of Far1p action requires elimination of FAR1 transcriptional regulation (by means of the GAL1 promoter) as well as N-terminal truncation. Thus, the cell cycle specificity of mating factor arrest may be largely due to cell cycle regulation of FAR1 transcription and protein stability.

scholarly journals A trans-Activation Domain in Yeast Heat Shock Transcription Factor Is Essential for Cell Cycle Progression during Stress

1999 ◽  
Vol 19 (1) ◽  
pp. 402-411 ◽  
Author(s):  
Kevin A. Morano ◽  
Nicholas Santoro ◽  
Keith A. Koch ◽  
Dennis J. Thiele
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Heat Shock ◽  
Cell Cycle Arrest ◽  
Transcriptional Activation ◽  
Heat Shock Transcription Factor ◽  
Yeast Cells ◽  
Activation Domain ◽  
Cycle Arrest ◽  
Carboxyl Terminal

ABSTRACT Gene expression in response to heat shock is mediated by the heat shock transcription factor (HSF), which in yeast harbors both amino- and carboxyl-terminal transcriptional activation domains. Yeast cells bearing a truncated form of HSF in which the carboxyl-terminal transcriptional activation domain has been deleted [HSF(1-583)] are temperature sensitive for growth at 37°C, demonstrating a requirement for this domain for sustained viability during thermal stress. Here we demonstrate that HSF(1-583) cells undergo reversible cell cycle arrest at 37°C in the G2/M phase of the cell cycle and exhibit marked reduction in levels of the molecular chaperone Hsp90. As in higher eukaryotes, yeast possesses two nearly identical isoforms of Hsp90: one constitutively expressed and one highly heat inducible. When expressed at physiological levels in HSF(1-583) cells, the inducible Hsp90 isoform encoded by HSP82 more efficiently suppressed the temperature sensitivity of this strain than the constitutively expressed gene HSC82, suggesting that different functional roles may exist for these chaperones. Consistent with a defect in Hsp90 production, HSF(1-583) cells also exhibited hypersensitivity to the Hsp90-binding ansamycin antibiotic geldanamycin. Depletion of Hsp90 from yeast cells wild type for HSF results in cell cycle arrest in both G1/S and G2/M phases, suggesting a complex requirement for chaperone function in mitotic division during stress.

The ΔN Isoform of the p73 Gene Is Induced during the G0→G1 Transition in Primary Human T Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3353-3353
Author(s):  
Constantinos Chronis ◽  
Alexander E. Smith ◽  
Stephen J. Orr ◽  
Kavita Raj ◽  
Ghulam J. Mufti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Transcriptional Activation ◽  
Cell Cycle Regulators ◽  
P53 Family ◽  
Transcriptional Activation Domain ◽  
Normal Tissues ◽  
Human T Cells ◽  
Normal Gene ◽  
Cycle Dependent

Abstract p73 is a member of the p53-family of transcription factors (p73, p53 and p63). A truncated form of p73 (ΔNp73) also exists that lacks the transcriptional activation domain and inhibits both p53 & p73. However, ΔNp73 transcripts have not been reported in normal tissues or peripheral blood. We now show for the first time that ΔNp73 mRNA and protein are not present in quiescent (G0), primary human T cells but are induced post the G0→G1 cell cycle commitment point following stimulation with anti-CD3/CD28 or PMA/ionomycin. The ΔNp73 transcript could be produced either by activation of a promoter in intron 3 or from the 5′ P1 promoter by alternative splicing. Bisulfite sequencing shows that the intron 3 promoter is hypermethylated in T cells in G0 and throughout the cell cycle while the 5′ P1 promoter remains largely unmethylated. 5′-RACE results with quiescent and stimulated T cells verify that ΔNp73 transcripts originate from the P1 promoter. Additionally, RT-PCR analyses show that the transcript originating from the P1 promoter is present in G0 and mature ΔNp73 mRNA is produced by cell cycle-dependent splicing during the G0→G1 transition. We investigated the function of ΔNp73 during G0→G1 by inhibiting its induction with two different siRNAs. Microarray analyses show that expression of mRNA encoding a number of cell cycle regulators like E2F1, TCFL2 and CDT1 during G0→G1 are dependent on ΔNp73 and ΔNp73 represses the expression of the pro-apoptotic PUMA, a known p73 target. We conclude that ΔNp73 is produced in normal, human T cells during cell cycle entry and regulates normal gene expression. Moreover, the intron 3 promoter is hypermethylated, the ΔNp73 transcript originates at the P1 promoter and ΔNp73 mRNA is produced by cell cycle-dependent splicing.

scholarly journals Transcriptional Activation in Yeast Cells Lacking Transcription Factor IIA

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1573-1581 ◽  
Author(s):  
Susanna Chou ◽  
Sukalyan Chatterjee ◽  
Mark Lee ◽  
Kevin Struhl
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Large Subunit ◽  
Yeast Cells ◽  
Specific Cell ◽  
Wild Type ◽  
Activation Domains ◽  
Cycle Arrest ◽  
General Transcription Factor

Abstract The general transcription factor IIA (TFIIA) forms a complex with TFIID at the TATA promoter element, and it inhibits the function of several negative regulators of the TATA-binding protein (TBP) subunit of TFIID. Biochemical experiments suggest that TFIIA is important in the response to transcriptional activators because activation domains can interact with TFIIA, increase recruitment of TFIID and TFIIA to the promoter, and promote isomerization of the TFIID-TFIIA-TATA complex. Here, we describe a double-shut-off approach to deplete yeast cells of Toa1, the large subunit of TFIIA, to <1% of the wild-type level. Interestingly, such TFIIA-depleted cells are essentially unaffected for activation by heat shock factor, Ace1, and Gal4-VP16. However, depletion of TFIIA causes a general two- to threefold decrease of transcription from most yeast promoters and a specific cell-cycle arrest at the G2-M boundary. These results indicate that transcriptional activation in vivo can occur in the absence of TFIIA.

scholarly journals A Yeast taf17 Mutant Requires the Swi6 Transcriptional Activator for Viability and Shows Defects in Cell Cycle-Regulated Transcription

Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1561-1576
Author(s):  
Neil Macpherson ◽  
Vivien Measday ◽  
Lynda Moore ◽  
Brenda Andrews
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Essential Gene ◽  
Temperature Sensitive ◽  
Permissive Temperature ◽  
Synthetic Lethal ◽  
Cycle Arrest ◽  
A Cell ◽  
Allelism Tests ◽  
Complementation Groups

Abstract In Saccharomyces cerevisiae, the Swi6 protein is a component of two transcription factors, SBF and MBF, that promote expression of a large group of genes in the late G1 phase of the cell cycle. Although SBF is required for cell viability, SWI6 is not an essential gene. We performed a synthetic lethal screen to identify genes required for viability in the absence of SWI6 and identified 10 complementation groups of swi6-dependent lethal mutants, designated SLM1 through SLM10. We were most interested in mutants showing a cell cycle arrest phenotype; both slm7-1 swi6Δ and slm8-1 swi6Δ double mutants accumulated as large, unbudded cells with increased 1N DNA content and showed a temperature-sensitive growth arrest in the presence of Swi6. Analysis of the transcript levels of cell cycle-regulated genes in slm7-1 SWI6 mutant strains at the permissive temperature revealed defects in regulation of a subset of cyclin-encoding genes. Complementation and allelism tests showed that SLM7 is allelic with the TAF17 gene, which encodes a histone-like component of the general transcription factor TFIID and the SAGA histone acetyltransferase complex. Sequencing showed that the slm7-1 allele of TAF17 is predicted to encode a version of Taf17 that is truncated within a highly conserved region. The cell cycle and transcriptional defects caused by taf17slm7-1 are consistent with the role of TAFIIs as modulators of transcriptional activation and may reflect a role for TAF17 in regulating activation by SBF and MBF.

scholarly journals Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 302 ◽  
Author(s):  
Xin Zhang ◽  
Yao Qin ◽  
Zhaohai Pan ◽  
Minjing Li ◽  
Xiaona Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cell Cycle Arrest ◽  
Phase Cell ◽  
G1 Phase ◽  
Therapeutic Effects ◽  
Human Gastric Cancer ◽  
Expression Levels ◽  
Cycle Arrest

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

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