scholarly journals The human histone gene expression regulator HBP/SLBP is required for histone and DNA synthesis, cell cycle progression and cell proliferation in mitotic cells

2004 ◽  
Vol 117 (25) ◽  
pp. 6043-6051 ◽  
Author(s):  
X. Zhao
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
Histone Gene ◽  
Cycle Progression ◽  
Histone Gene Expression ◽  
Mitotic Cells

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

scholarly journals 6-Methylsulfinylhexyl Isothiocyanate Inhibits Cell Cycle Progression in Quiescent Jb6 Cells Stimulated with Epidermal Growth Factor

2021 ◽  
pp. 19-28
Author(s):  
Takashi Hashimoto ◽  
Maki Kobayashi ◽  
Kazuki Kanazawa
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Cycle Progression ◽  
Epidermal Growth ◽  
Jb6 Cells

Objective: The effects of 6-MSITC on cell cycle progression were investigated in quiescent mouse epidermal JB6 cells. Background: 6-Methylsulfinylhexyl isothiocyanate (6-MSITC) derived from wasabi (Wasabia japonica) has been reported to prevent tumor development in vivo. Material and methods: Treatment with epidermal growth factor (EGF) to quiescent JB6 cells, which were serum-starved for 36 h, promoted cell cycle progression from the G0/G1 phase to the S phase. Effects of pretreatment with 6-MSITC on cell cycle progression were estimated by flowcytometry and real-time RT-PCR. Results: Pretreatment with 6-MSITC at 0.25-1.0 μg/ml prior to the growth stimulation with EGF significantly inhibited cell cycle progression. Pretreatment with 6-MSITC inhibited the gene expression of DNA synthesis-related proteins cyclin A2, dumbbell former 4, and proliferating cell nuclear antigen. Conclusion: These results showed that 6-MSITC inhibits cell cycle progression in quiescent cells, accompanied by the inhibition of gene expression of DNA synthesis proteins.

scholarly journals Distinct Signaling Pathways Mediate Stimulation of Cell Cycle Progression and Prevention of Apoptotic Cell Death by Estrogen in Rat Pituitary Tumor PR1 Cells

2003 ◽  
Vol 14 (12) ◽  
pp. 5051-5059 ◽  
Author(s):  
Simona Caporali ◽  
Manami Imai ◽  
Lucia Altucci ◽  
Massimo Cancemi ◽  
Silvana Caristi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Death ◽  
Dna Synthesis ◽  
Cell Survival ◽  
Pituitary Tumor ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Rat Pituitary ◽  
Stimulation Of

Estrogens control cell growth and viability in target cells via an interplay of genomic and extragenomic pathways not yet elucidated. Here, we show evidence that cell proliferation and survival are differentially regulated by estrogen in rat pituitary tumor PR1 cells. Pico- to femtomolar concentrations of 17β-estradiol (E2) are sufficient to foster PR1 cell proliferation, whereas nanomolar concentrations of the same are needed to prevent cell death that occurs at a high rate in these cells in the absence of hormone. Activation of endogenous (PRL) or transfected estrogen-responsive genes occurs at the same, higher concentrations of E2 required to promote cell survival, whereas stimulation of cyclin D3 expression and DNA synthesis occur at lower E2 concentrations. Similarly, the pure antiestrogen ICI 182,780 inhibits estrogen response element-dependent trans-activation and cell death more effectively than cyclin-cdk activity, G1-S transition, or DNA synthesis rate. In antiestrogen-treated and/or estrogen-deprived cells, death is due predominantly to apoptosis. Estrogen-induced cell survival, but not E2-dependent cell cycle progression, can be prevented by an inhibitor of c-Src kinase or by blockade of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway. These data indicate the coexistence of two distinguishable estrogen signaling pathways in PR1 cells, characterized by different functions and sensitivity to hormones and antihormones.

scholarly journals High Glucose Concentration Alters Cell Proliferation Dynamics in Human Hepatoma Cells

1999 ◽  
Vol 18 (5) ◽  
pp. 297-306 ◽  
Author(s):  
Prathibha S. Rao ◽  
Beverly D. Lyn-Cook ◽  
Neil A. Littlefield ◽  
Harihara M. Mehendale
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Lactate Dehydrogenase ◽  
Dna Synthesis ◽  
High Glucose ◽  
Glucose Concentration ◽  
Cell Cycle Progression ◽  
Treated Group ◽  
High Glucose Concentration ◽  
Cycle Progression

The aim of this study was to develop an in vitro model to investigate the molecular mechanisms of glucose-induced inhibition of cell proliferation. HuH7 cells were grown in the presence or absence of glucose for 7 days and cell proliferation was stimulated by exposure to thioacetamide. Lactate dehydrogenase leakage and 3H-thymidine incorporation were used as indices of toxicity and DNA synthesis, respectively. Cell cycle progression and protooncogene expression was monitored by flow cytometry and slot-blot analyses. Toxicity caused by thioacetamide regressed with time in the presence of 11 mM glucose (control). However, in the presence of 28 mM glucose, sustained toxicity was evident as mirrored by lactate dehydrogenase leakage. Peak DNA synthesis noted at 48 hours in the thioacetamide-treated group (11 mM glucose) was significantly diminished in the presence of 28 mM glucose. Increased c-myc expression was observed as early as 30 minutes in the thioacetamide-treated group. When cells were exposed to 28 mM glucose, c-myc expression was delayed and diminished. Methylation profile studies revealed no appreciable changes, but c-myc was significantly amplified in the control, thioacetamide-, and in the presence of 28 mM of glucose-treated groups which correlated with mRNA changes in these groups. In the glucose-pretreated group (28 mM) significant amplification of the c-myc gene was observed at later time points but there was no change in the mRNA expression, indicating that the expression was delayed. This study shows that high glucose concentrations diminish DNA synthesis and cell cycle progression normally stimulated by thioacetamide. It is concluded that high glucose concentration causes cell cycle arrest via perturbation in protooncogene expression and hence the use of high glucose concentrations in therapy should be carefully examined in situations where postsurgical healing and healing after xenobiotic-induced injury are encountered.

scholarly journals Distinct replication-independent and -dependent phases of histone gene expression during the Physarum cell cycle.

1987 ◽  
Vol 7 (5) ◽  
pp. 1933-1937 ◽  
Author(s):  
J J Carrino ◽  
V Kueng ◽  
R Braun ◽  
T G Laffler
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Replication ◽  
Dna Synthesis ◽  
S Phase ◽  
Histone Gene ◽  
Histone Mrna ◽  
Histone Gene Expression ◽  
Tightly Coupled ◽  
G2 Phase

During the S phase of the cell cycle, histone gene expression and DNA replication are tightly coupled. In mitotically synchronous plasmodia of the myxomycete Physarum polycephalum, which has no G1 phase, histone mRNA synthesis begins in mid-G2 phase. Although histone gene transcription is activated in the absence of significant DNA synthesis, our data demonstrate that histone gene expression became tightly coupled to DNA replication once the S phase began. There was a transition from the replication-independent phase to the replication-dependent phase of histone gene expression. During the first phase, histone mRNA synthesis appears to be under direct cell cycle control; it was not coupled to DNA replication. This allowed a pool of histone mRNA to accumulate in late G2 phase, in anticipation of future demand. The second phase began at the end of mitosis, when the S phase began, and expression became homeostatically coupled to DNA replication. This homeostatic control required continuing protein synthesis, since cycloheximide uncoupled transcription from DNA synthesis. Nuclear run-on assays suggest that in P. polycephalum this coupling occurs at the level of transcription. While histone gene transcription appears to be directly switched on in mid-G2 phase and off at the end of the S phase by cell cycle regulators, only during the S phase was the level of transcription balanced with the rate of DNA synthesis.

Distinct replication-independent and -dependent phases of histone gene expression during the Physarum cell cycle

1987 ◽  
Vol 7 (5) ◽  
pp. 1933-1937
Author(s):  
J J Carrino ◽  
V Kueng ◽  
R Braun ◽  
T G Laffler
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Replication ◽  
Dna Synthesis ◽  
S Phase ◽  
Histone Gene ◽  
Histone Mrna ◽  
Histone Gene Expression ◽  
Tightly Coupled ◽  
G2 Phase

During the S phase of the cell cycle, histone gene expression and DNA replication are tightly coupled. In mitotically synchronous plasmodia of the myxomycete Physarum polycephalum, which has no G1 phase, histone mRNA synthesis begins in mid-G2 phase. Although histone gene transcription is activated in the absence of significant DNA synthesis, our data demonstrate that histone gene expression became tightly coupled to DNA replication once the S phase began. There was a transition from the replication-independent phase to the replication-dependent phase of histone gene expression. During the first phase, histone mRNA synthesis appears to be under direct cell cycle control; it was not coupled to DNA replication. This allowed a pool of histone mRNA to accumulate in late G2 phase, in anticipation of future demand. The second phase began at the end of mitosis, when the S phase began, and expression became homeostatically coupled to DNA replication. This homeostatic control required continuing protein synthesis, since cycloheximide uncoupled transcription from DNA synthesis. Nuclear run-on assays suggest that in P. polycephalum this coupling occurs at the level of transcription. While histone gene transcription appears to be directly switched on in mid-G2 phase and off at the end of the S phase by cell cycle regulators, only during the S phase was the level of transcription balanced with the rate of DNA synthesis.

scholarly journals STAU2 Protein Level is Controlled by Caspases and the CHK1 Pathway and Regulates Cell Cycle Progression in the Non-transformed hTERT-RPE1 Cells

2020 ◽  
Author(s):  
Lionel Conde ◽  
Remy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

Abstract Background: Staufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from the STAU2 gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation. Results: CRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway dissociates STAU1 from proteins involved in translation and RNA metabolism. Conclusions: These results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. This novel function of STAU2 is regulated by caspases and by the kinase CHK1 pathway.

scholarly journals Exogenous pyruvate represses histone gene expression and inhibits cancer cell proliferation via the NAMPT–NAD+–SIRT1 pathway

2019 ◽  
Vol 47 (21) ◽  
pp. 11132-11150 ◽  
Author(s):  
Rui Ma ◽  
Yinsheng Wu ◽  
Yansheng Zhai ◽  
Bicheng Hu ◽  
Wei Ma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Histone Gene ◽  
Gene Promoters ◽  
Cancer Cell Proliferation ◽  
Signal Molecule ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Histone Gene Expression

Abstract Pyruvate is a glycolytic metabolite used for energy production and macromolecule biosynthesis. However, little is known about its functions in tumorigenesis. Here, we report that exogenous pyruvate inhibits the proliferation of different types of cancer cells. This inhibitory effect of pyruvate on cell growth is primarily attributed to its function as a signal molecule to repress histone gene expression, which leads to less compact chromatin and misregulation of genome-wide gene expression. Pyruvate represses histone gene expression by inducing the expression of NAD+ biosynthesis enzyme, nicotinamide phosphoribosyltransferase (NAMPT) via myocyte enhancer factor 2C (MEF2C), which then increases NAD+ levels and activates the histone deacetylase activity of SIRT1. Chromatin immunoprecipitation analysis indicates that pyruvate enhances SIRT1 binding at histone gene promoters where it reduces histone acetylation. Although pyruvate delays cell entry into S phase, pyruvate represses histone gene expression independent of cell cycle progression. Moreover, we find that administration of pyruvate reduces histone expression and retards tumor growth in xenograft mice without significant side effects. Using tissues from cervical and lung cancer patients, we find intracellular pyruvate concentrations inversely correlate with histone protein levels. Together, we uncover a previously unknown function of pyruvate in regulating histone gene expression and cancer cell proliferation.

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