scholarly journals Cell cycle inhibitor Whi5 records environmental information to coordinate growth and division in yeast

2019 ◽  
Author(s):  
Yimiao Qu ◽  
Jun Jiang ◽  
Xiang Liu ◽  
Ping Wei ◽  
Xiaojing Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Doubling Time ◽  
Optimal Timing ◽  
Proliferating Cells ◽  
Cell Cycle Entry ◽  
Cellular Decision Making ◽  
Need To Evaluate ◽  
A Cell ◽  
Made In

SUMMARYProliferating cells need to evaluate the environment to determine the optimal timing for cell cycle entry, which is essential for coordinating cell division and growth. In the budding yeast Saccharomyces cerevisiae, the commitment to the next round of division is made in G1 at the Start, triggered by the inactivation of the inhibitor Whi5 through multiple mechanisms. However, how a cell reads environmental condition and uses this information to regulate Start is poorly understood. Here, we show that Whi5 is a key environmental indicator and plays a crucial role in coordinating cell growth and division. We found that under a variety of nutrient and stress conditions, the concentration of Whi5 in G1 is proportional to the doubling time in the environment. Thus, under a poorer condition a longer doubling time results in a higher Whi5 concentration, which in turn delays the next cell cycle entry to ensure sufficient cell growth. In addition, the coordination between division and the environment is further fine-tuned in G1 by environmentally dependent G1 cyclin-Cdk1 contribution and Whi5 threshold at Start. Our results show that Whi5 serves as an environmental ‘memory’ and that the cell adopts a simple and elegant mechanism to achieve an adaptive cellular decision making.

scholarly journals PP2ARts1 is a master regulator of pathways that control cell size

2014 ◽  
Vol 204 (3) ◽  
pp. 359-376 ◽  
Author(s):  
Jessica Zapata ◽  
Noah Dephoure ◽  
Tracy MacDonough ◽  
Yaxin Yu ◽  
Emily J. Parnell ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Size ◽  
Control Cell ◽  
Size Control ◽  
Regulatory Subunit ◽  
Delay Cell ◽  
Cell Cycle Entry ◽  
G1 Cyclin

Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth.

S-phase-specific expression of the Mad3 gene in proliferating and differentiating cells

2001 ◽  
Vol 359 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Elizabeth J. FOX ◽  
Stephanie C. WRIGHT
Keyword(s):  
Cell Cycle ◽  
Cellular Proliferation ◽  
Cultured Cells ◽  
S Phase ◽  
Proliferating Cells ◽  
Specific Expression ◽  
Related Function ◽  
Erythroleukemia Cells ◽  
A Cell ◽  
Pass Through

The Myc/Max/Mad transcription factor network plays a central role in the control of cellular proliferation, differentiation and apoptosis. In order to elucidate the biological function of Mad3, we have analysed the precise temporal patterns of Mad3 mRNA expression during the cell cycle and differentiation in cultured cells. We show that Mad3 is induced at the G1/S transition in proliferating cells; expression persists throughout S-phase, and then declines as cells pass through G2 and mitosis. The expression pattern of Mad3 is coincident with that of Cdc2 throughout the cell cycle. In contrast, the expression of Mad3 during differentiation of cultured mouse erythroleukemia cells shows two transient peaks of induction. The first of these occurs at the onset of differentiation, and does not correlate with the S-phase of the cell cycle, whereas the second is coincident with the S-phase burst that precedes the terminal stages of differentiation. Our results therefore suggest that Mad3 serves a cell-cycle-related function in both proliferating and differentiating cells, and that it may also have a distinct role at various stages of differentiation.

scholarly journals Growth-dependent signals drive an increase in early G1 cyclin concentration to link cell cycle entry with cell growth

2020 ◽  
Author(s):  
Robert A. Sommer ◽  
Jerry T. DeWitt ◽  
Raymond Tan ◽  
Douglas R. Kellogg
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Budding Yeast ◽  
Control Cell ◽  
Transcriptional Repressor ◽  
Cell Cycle Entry ◽  
G1 Cyclin

AbstractEntry into the cell cycle occurs only when sufficient growth has occurred. In budding yeast, the cyclin Cln3 initiates cell cycle entry by inactivating a transcriptional repressor called Whi5. Growth-dependent changes in the concentrations of Cln3 or Whi5 have been proposed to link cell cycle entry to cell growth. However, there are conflicting reports regarding the behavior and roles of Cln3 and Whi5. Here, we found no evidence that changes in the concentration of Whi5 play a major role in controlling cell cycle entry. Rather, the data suggest that cell growth triggers cell cycle entry by driving an increase in the concentration of Cln3. We further found that accumulation of Cln3 is dependent upon homologs of mammalian SGK kinases that play roles in control of cell growth and size. Together, the data are consistent with models in which Cln3 serves as the crucial link between the cell cycle and signals that control cell growth and size.

scholarly journals THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jing Zhang ◽  
Huahua Zhang ◽  
Haiyan Shi ◽  
Fenghui Wang ◽  
Juan Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cancer Cell Growth ◽  
Protein Levels ◽  
Cycle Arrest ◽  
A Cell ◽  
Regulation Mechanisms ◽  
Cell Growth Suppression

We aim to investigate the role of THAP11 (thanatos-associated protein11) in gastric cancer and its regulation mechanisms. THAP11 expression was analyzed in 51 pairs of GC tissues and the corresponding paracancerous tissues by qRT-PCR and Western blot. After THAP11 was overexpressed or knocked-down, cell proliferation, cell cycle, and apoptosis were detected in MKN-45 cells. We found that THAP11 was significantly downregulated in GC tissues and GC cell lines. Functionally, THAP11 overexpression markedly inhibited cell growth, induced G1/G0 cell-cycle arrest, and promoted cell apoptosis of MKN-45 cells, while silencing of THAP11 led to increased cell growth, increased DNA synthesis, and inhibited apoptosis. In addition, THAP11 negatively regulated the expression of c-Myc, decreased cyclinD1 protein, and increased p27 and p21 protein levels. We also found cell growth suppression induced by THAP11 was rescued by c-Myc overexpression, further confirming that THAP11 suppresses gastric cancer cell growth via the c-Myc pathway. THAP11 acts as a cell growth suppressor and exerts its role possibly through negatively regulating c-Myc pathway in gastric cancer.

scholarly journals Pocket Protein Complexes Are Recruited to Distinct Targets in Quiescent and Proliferating Cells

2005 ◽  
Vol 25 (18) ◽  
pp. 8166-8178 ◽  
Author(s):  
Egle Balciunaite ◽  
Alexander Spektor ◽  
Nathan H. Lents ◽  
Hugh Cam ◽  
Hein te Riele ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Regulatory Networks ◽  
Protein Complexes ◽  
Proliferating Cells ◽  
Quiescent Cells ◽  
Pocket Protein ◽  
Genome Wide ◽  
E2f Transcription Factor ◽  
A Cell ◽  
Cycle Dependent

ABSTRACT Biochemical and genetic studies have determined that retinoblastoma protein (pRB) tumor suppressor family members have overlapping functions. However, these studies have largely failed to distinguish functional differences between the highly related p107 and p130 proteins. Moreover, most studies pertaining to the pRB family and its principal target, the E2F transcription factor, have focused on cells that have reinitiated a cell cycle from quiescence, although recent studies suggest that cycling cells exhibit layers of regulation distinct from mitogenically stimulated cells. Using genome-wide chromatin immunoprecipitation, we show that there are distinct classes of genes directly regulated by unique combinations of E2F4, p107, and p130, including a group of genes specifically regulated in cycling cells. These groups exhibit both distinct histone acetylation signatures and patterns of mammalian Sin3B corepressor recruitment. Our findings suggest that cell cycle-dependent repression results from recruitment of an unexpected array of diverse complexes and reveals specific differences between transcriptional regulation in cycling and quiescent cells. In addition, factor location analyses have, for the first time, allowed the identification of novel and specific targets of the highly related transcriptional regulators p107 and p130, suggesting new and distinct regulatory networks engaged by each protein in continuously cycling cells.

Human monoclonal antibody BT32/A6 and a cell cycle—independent glioma-associated surface antigen

1995 ◽  
Vol 82 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Michael D. Dan ◽  
Elizabeth M. Earley ◽  
Mark C. Griffin ◽  
Pradip K. Maiti ◽  
Ashok K. Prashar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Growth Rate ◽  
Cell Growth ◽  
Surface Antigen ◽  
Immunoglobulin M ◽  
Cell Growth Rate ◽  
Culture Viability ◽  
A Cell

✓ The purpose of this study was to ascertain how various growth parameters may influence the labeling of SK-MG-1, a human glioma cell line, by BT32/A6, a human immunoglobulin M monoclonal antibody (MAb). By growing SKMG-1 cells at different culture split ratios, significant trends in cell growth rate, culture viability, and cell cycle state were produced. Labeling of SK-MG-1 cells by BT32/A6, however, was shown to be unaffected by culture split ratio (p > 0.05) and is therefore independent of cell growth rate, culture viability, and cell cycle state. Using flow cytometry and fluorescence-activated cell sorting, BT32/A6 was shown to label a cell surface antigen on viable, clonogenic cells of SK-MG-1. Approximately 100% of SK-MG-1 cells were shown by flow cytometry to express the BT32/A6 antigen. The recognition of a glioma-associated, cell cycle-independent surface antigen by MAb BT32/A6 makes it a promising candidate for further studies aimed at elucidating its usefulness as an adjunct in the treatment of human malignant gliomas.

Tubulin polyglutamylase: isozymic variants and regulation during the cell cycle in HeLa cells

1999 ◽  
Vol 112 (23) ◽  
pp. 4281-4289 ◽  
Author(s):  
C. Regnard ◽  
E. Desbruyeres ◽  
P. Denoulet ◽  
B. Edde
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
Molecular Motors ◽  
Dependent Manner ◽  
Proliferating Cells ◽  
Beta Tubulin ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
A Cell ◽  
Cycle Dependent

Polyglutamylation is a posttranslational modification of tubulin that is very common in neurons and ciliated or flagellated cells. It was proposed to regulate the binding of microtubule associated proteins (MAPs) and molecular motors as a function of the length of the polyglutamyl side-chain. Though much less common, this modification of tubulin also occurs in proliferating cells like HeLa cells where it is associated with centrioles and with the mitotic spindle. Recently, we partially purified tubulin polyglutamylase from mouse brain and described its enzymatic properties. In this work, we focused on tubulin polyglutamylase activity from HeLa cells. Our results support the existence of a tubulin polyglutamylase family composed of several isozymic variants specific for alpha- or beta-tubulin subunits. In the latter case, the specificity probably also concerns the different beta-tubulin isotypes. Interestingly, we found that tubulin polyglutamylase activity is regulated in a cell cycle dependent manner and peaks in G(2)-phase while the level of glutamylated tubulin peaks in mitosis. Consistent results were obtained by treating the cells with hydroxyurea, nocodazole or taxotere. In particular, in mitotic cells, tubulin polyglutamylase activity was always low while glutamylation level was high. Finally, tubulin polyglutamylase activity and the level of glutamylated tubulin appeared to be inversely related. This paradox suggests a complex regulation of both tubulin polyglutamylase and the reverse deglutamylase activity.

scholarly journals Aneuploid yeast strains exhibit defects in cell growth and passage through START

2013 ◽  
Vol 24 (9) ◽  
pp. 1274-1289 ◽  
Author(s):  
Rebecca R. Thorburn ◽  
Christian Gonzalez ◽  
Gloria A. Brar ◽  
Stefan Christen ◽  
Thomas M. Carlile ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Cell Proliferation ◽  
Growth Defect ◽  
Cell Cycle Entry ◽  
Yeast Strains ◽  
Additional Chromosome ◽  
A Cell ◽  
Cellular Stresses ◽  
Haploid Karyotype

Aneuploidy, a chromosome content that is not a multiple of the haploid karyotype, is associated with reduced fitness in all organisms analyzed to date. In budding yeast aneuploidy causes cell proliferation defects, with many different aneuploid strains exhibiting a delay in G1, a cell cycle stage governed by extracellular cues, growth rate, and cell cycle events. Here we characterize this G1 delay. We show that 10 of 14 aneuploid yeast strains exhibit a growth defect during G1. Furthermore, 10 of 14 aneuploid strains display a cell cycle entry delay that correlates with the size of the additional chromosome. This cell cycle entry delay is due to a delayed accumulation of G1 cyclins that can be suppressed by supplying cells with high levels of a G1 cyclin. Our results indicate that aneuploidy frequently interferes with the ability of cells to grow and, as with many other cellular stresses, entry into the cell cycle.

scholarly journals L2DTL, a cell cycle regulated gene is essential to tumor cell growth

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Hung‐Wei Pan ◽  
Mei‐Ling Chen ◽  
Ray‐Hwang Yuan
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
A Cell
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