scholarly journals The TRF2 General Transcription Factor Is a Key Regulator of Cell Cycle Progression

2020 ◽  
Author(s):  
Adi Kedmi ◽  
Anna Sloutskin ◽  
Natalie Epstein ◽  
Lital Gasri-Plotnitsky ◽  
Debby Ickowicz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Transcription Factor ◽  
Cell Cycle Progression ◽  
Binding Protein ◽  
Cyclin E ◽  
Mass Spectrometry Analysis ◽  
Related Factor ◽  
Cycle Progression ◽  
General Transcription Factor

AbstractTRF2 (TATA-box-binding protein-related factor 2) is an evolutionarily conserved general transcription factor that is essential for embryonic development of Drosophila melanogaster, C. elegans, zebrafish and Xenopus. Nevertheless, the cellular processes that are regulated by TRF2 are largely underexplored.Here, using Drosophila Schneider cells as a model, we discovered that TRF2 regulates cell cycle progression. Using flow cytometry, high-throughput microscopy and advanced imaging-flow cytometry, we demonstrate that TRF2 knockdown regulates cell cycle progression and exerts distinct effects on G1 and specific mitotic phases. RNA-seq analysis revealed that TRF2 regulates the expression of Cyclin E and the mitotic cyclins, Cyclin A, Cyclin B and Cyclin B3, but not Cyclin D or Cyclin C. To identify proteins that could account for the observed regulation of these cyclin genes, we searched for TRF2-interacting proteins. Interestingly, mass spectrometry analysis of TRF2-containing complexes identified GFZF, a nuclear glutathione S-transferase implicated in cell cycle regulation, and Motif 1 binding protein (M1BP). Furthermore, available ChIP-exo data revealed that TRF2, GFZF and M1BP co-occupy the promoters of TRF2-regulated genes. Using RNAi to knockdown the expression of either M1BP, GFZF, TRF2 or their combinations, we demonstrate that although GFZF and M1BP interact with TRF2, it is TRF2, rather than GFZF or M1BP, that is the main factor regulating the expression of Cyclin E and the mitotic cyclins. Taken together, our findings uncover a critical and unanticipated role of a general transcription factor as a key regulator of cell cycle.

scholarly journals TATA-Binding Protein-Like Protein (TLP/TRF2/TLF) Negatively Regulates Cell Cycle Progression and Is Required for the Stress-Mediated G2 Checkpoint

2003 ◽  
Vol 23 (12) ◽  
pp. 4107-4120 ◽  
Author(s):  
Miho Shimada ◽  
Tomoyoshi Nakadai ◽  
Taka-aki Tamura
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Stress Response ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Cycle Progression ◽  
Stress Dependent ◽  
Dt40 Cells

ABSTRACT The TATA-binding protein (TBP) is a universal transcription factor required for all of the eukaryotic RNA polymerases. In addition to TBP, metazoans commonly express a distantly TBP-related protein referred to as TBP-like protein (TLP/TRF2/TLF). Although the function of TLP in transcriptional regulation is not clear, it is known that TLP is required for embryogenesis and spermiogenesis. In the present study, we investigated the cellular functions of TLP by using TLP knockout chicken DT40 cells. TLP was found to be dispensable for cell growth. Unexpectedly, TLP-null cells exhibited a 20% elevated cell cycle progression rate that was attributed to shortening of the G2 phase. This indicates that TLP functions as a negative regulator of cell growth. Moreover, we found that TLP mainly existed in the cytoplasm and was translocated to the nucleus restrictedly at the G2 phase. Ectopic expression of nuclear localization signal-carrying TLP resulted in an increase (1.5-fold) in the proportion of cells remaining in the G2/M phase and apoptotic state. Notably, TLP-null cells showed an insufficient G2 checkpoint when the cells were exposed to stresses such as UV light and methyl methanesulfonate, and the population of apoptotic cells after stresses decreased to 40%. These phenomena in G2 checkpoint regulation are suggested to be p53 independent because p53 does not function in DT40 cells. Moreover, TLP was transiently translocated to the nucleus shortly (15 min) after stress treatment. The expression of several stress response and cell cycle regulatory genes drifted in a both TLP- and stress-dependent manner. Nucleus-translocating TLP is therefore thought to work by checking cell integrity through its transcription regulatory ability. TLP is considered to be a signal-transducing transcription factor in cell cycle regulation and stress response.

scholarly journals NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes

Cell Cycle ◽  
2016 ◽  
Vol 15 (17) ◽  
pp. 2346-2359 ◽  
Author(s):  
Leonardo K. Teixeira ◽  
Nina Carrossini ◽  
Cristiane Sécca ◽  
José E. Kroll ◽  
Déborah C. DaCunha ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
B Lymphocytes ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression

scholarly journals The GTP-binding Protein Rho1p Is Required for Cell Cycle Progression and Polarization of the Yeast Cell

1999 ◽  
Vol 146 (2) ◽  
pp. 373-387 ◽  
Author(s):  
Jana Drgonová ◽  
Tomás Drgon ◽  
Dong-Hyun Roh ◽  
Enrico Cabib
Keyword(s):  
Cell Cycle ◽  
Yeast Cell ◽  
Cell Cycle Progression ◽  
Binding Protein ◽  
Cell Polarization ◽  
Nonpermissive Temperature ◽  
Gtp Binding Protein ◽  
Cycle Progression ◽  
Glucan Synthase ◽  
Gtp Binding

Previous work showed that the GTP-binding protein Rho1p is required in the yeast, Saccharomyces cerevisiae, for activation of protein kinase C (Pkc1p) and for activity and regulation of β(1→3)glucan synthase. Here we demonstrate a hitherto unknown function of Rho1p required for cell cycle progression and cell polarization. Cells of mutant rho1E45I in the G1 stage of the cell cycle did not bud at 37°C. In those cells actin reorganization and recruitment to the presumptive budding site did not take place at the nonpermissive temperature. Two mutants in adjacent amino acids, rho1V43T and rho1F44Y, showed a similar behavior, although some budding and actin polarization occurred at the nonpermissive temperature. This was also the case for rho1E45I when placed in a different genetic background. Cdc42p and Spa2p, two proteins that normally also move to the bud site in a process independent from actin organization, failed to localize properly in rho1E45I. Nuclear division did not occur in the mutant at 37°C, although replication of DNA proceeded slowly. The rho1 mutants were also defective in the formation of mating projections and in congregation of actin at the projections in the presence of mating pheromone. The in vitro activity of β(1→3)glucan synthase in rho1 E45I, although diminished at 37°C, appeared sufficient for normal in vivo function and the budding defect was not suppressed by expression of a constitutively active allele of PKC1. Reciprocally, when Pkc1p function was eliminated by the use of a temperature-sensitive mutation and β(1→3)glucan synthesis abolished by an echinocandin-like inhibitor, a strain carrying a wild-type RHO1 allele was able to produce incipient buds. Taken together, these results reveal a novel function of Rho1p that must be executed in order for the yeast cell to polarize.

scholarly journals Radiation-induced cell cycle perturbations: a computational tool validated with flow-cytometry data

2020 ◽  
Author(s):  
Leonardo Lonati ◽  
Sofia Barbieri ◽  
Isabella Guardamagna ◽  
Andrea Ottolenghi ◽  
Giorgio Baiocco
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Ionizing Radiation ◽  
Radiation Exposure ◽  
Cell Cycle Progression ◽  
Model Parameters ◽  
Clinical Use ◽  
Transition Rates ◽  
Computational Tool ◽  
Cycle Progression

AbstractCell cycle progression can be studied with computational models that allow to describe and predict its perturbation by agents as ionizing radiation or drugs. Such models can then be integrated in tools for pre-clinical/clinical use, e.g. to optimize kinetically-based administration protocols of radiation therapy and chemotherapy.We present a deterministic compartmental model, specifically reproducing how cells that survive radiation exposure are distributed in the cell cycle as a function of dose and time after exposure. Model compartments represent the four cell-cycle phases, as a fuction of DNA content and time. A system of differential equations, whose parameters represent transition rates, division rate and DNA synthesis rate, describes the temporal evolution. Initial model inputs are data from unexposed cells in exponential growth. Perturbation is implemented as an alteration of model parameters that allows to best reproduce cell-cycle profiles post-irradiation. The model is validated with dedicated in vitro measurements on human lung fibroblasts (IMR90). Cells were irradiated with 2 and 5 Gy with a Varian 6 MV Clinac at IRCCS Maugeri. Flow cytometry analysis was performed at the RadBioPhys Laboratory (University of Pavia), obtaining cell percentages in each of the four phases in all studied conditions up to 72 hours post-irradiation.Cells show early G2-phase block (increasing in duration as dose increases) and later G1-phase accumulation. For each condition, we identified the best sets of model parameters that lead to a good agreement between model and experimental data, varying transition rates from G1- to S- and from G2- to M-phase.This work offers a proof-of-concept validation of the new computational tool, opening to its future development and, in perspective, to its integration in a wider framework for clinical use.Author summaryWe implemented a computational model able to describe how the progression in the cell cycle is perturbed when cells are exposed to ionizing radiation. It is known that radiation causes delays or arrest in cell cycle progression, and also that cells that are in different phases of the cycle at the time of exposure show different sensitivity to radiation. Chemotherapeutic drugs also affect cell cycle, and their action can be phase-specific. These findings can be exploited to find the optimal protocol of a combined radiotherapy/chemotherapy cancer treatment: to this aim, we need to know not only the effectiveness of an agent (dose/drug) in terms of cell killing, but also how surviving cells are distributed in the cell cycle. With the model we present, this information can be reproduced as a function of dose and time after radiation exposure. To test the model performance we measured distributions of cells in different phases of the cycle (using flow-cytometry) for human healthy fibroblast cells exposed to X-rays. The results of this work constitute a first step for further development of our model and its future integration in a tool for pre-clinical/clinical use.

A Novel Function for Cyclin E in Cell Cycle Progression

2007 ◽  
pp. 31-39
Author(s):  
Yan Geng ◽  
Youngmi Lee ◽  
Markus Welcker ◽  
Jherek Swanger ◽  
Agnieszka Zagozdzon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression

scholarly journals Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Development ◽  
2011 ◽  
Vol 138 (11) ◽  
pp. 2223-2234 ◽  
Author(s):  
P. M. Fox ◽  
V. E. Vought ◽  
M. Hanazawa ◽  
M.-H. Lee ◽  
E. M. Maine ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression ◽  
C Elegans ◽  
Proliferative Cell

scholarly journals Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel−/− B cells

Oncogene ◽  
2003 ◽  
Vol 22 (52) ◽  
pp. 8472-8486 ◽  
Author(s):  
Shuhua Cheng ◽  
Constance Yu Hsia ◽  
Gustavo Leone ◽  
Hsiou-Chi Liou
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression ◽  
Induce Cell Cycle Progression

scholarly journals The TIA1 RNA-Binding Protein Family Regulates EIF2AK2-Mediated Stress Response and Cell Cycle Progression

2018 ◽  
Vol 69 (4) ◽  
pp. 622-635.e6 ◽  
Author(s):  
Cindy Meyer ◽  
Aitor Garzia ◽  
Michael Mazzola ◽  
Stefanie Gerstberger ◽  
Henrik Molina ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stress Response ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Family ◽  
Cycle Progression

Growth Characteristics of Anaerobically Treated Early and Late S-Period of Ehrlich Ascites Tumor Cells after Reaeration

1983 ◽  
Vol 38 (3-4) ◽  
pp. 313-318 ◽  
Author(s):  
Rainer Merz ◽  
Friedhelm Schneider
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Ehrlich Ascites Tumor Cells ◽  
Ascites Tumor ◽  
Cycle Progression ◽  
Ehrlich Ascites ◽  
Main Fraction ◽  
S Period

Utilizing centrifugal elutriation, early and late S-phase cells were separated from 4, 8 and 12 h anaerobically cultured Ehrlich Ascites tumor cells strain Karzel. The cytokinetic properties of these fractions after reaeration were studied by flow cytometry and the BrdU-H 33258-technique of flow cytometry. After a 4 h period of anaerobiosis, growth of early S-phase cells is not changed, 8 h deprivation of oxygen causes a delay of cell cycle progression, while the main fraction of 12 h anaerobically treated early S-populations did not divide after reaeration within 24 h. In comparison to early S-phase cells the cell cycle progression of the main fraction of late S-period is accelerated after a 4 h exclusion of oxygen. A fraction of 8 h anaerobically pretreated late S-cells continues to cycle, but a considerable number reinitiates DNA synthesis without preceeding division. Cells with DNA content up to 8 c are detected by flow cytometry. 12 h anaerobically cultured late S-cells do not divide after reaeration, a large number of these cells starts again to synthesize DNA. A considerable part of tetraploid cells retain viability, divide and enter a new cell cycle, another part of the cells disintegrates

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