scholarly journals p21 in Cancer Research

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1178 ◽  
Author(s):  
Shamloo ◽  
Usluer
Keyword(s):  
Cell Cycle ◽  
Cancer Research ◽  
Tumor Suppressor Function ◽  
Therapeutic Approaches ◽  
Cell Cycle Inhibitor ◽  
Cycle Arrest ◽  
Cancer Field ◽  
A Cell ◽  
P53 Status

p21 functions as a cell cycle inhibitor and anti-proliferative effector in normal cells, and is dysregulated in some cancers. Earlier observations on p21 knockout models emphasized the role of this protein in cell cycle arrest under the p53 transcription factor activity. Although tumor-suppressor function of p21 is the most studied aspect of this protein in cancer, the role of p21 in phenotypic plasticity and its oncogenic/anti-apoptotic function, depending on p21 subcellular localization and p53 status, have been under scrutiny recently. Basic science and translational studies use precision gene editing to manipulate p21 itself, and proteins that interact with it; these studies have led to regulatory/functional/drug sensitivity discoveries as well as therapeutic approaches in cancer field. In this review, we will focus on targeting p21 in cancer research and its potential in providing novel therapies.

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 The Role of Redox Proteins in Arresting Proliferation of Breast Epithelial Cells Under Oxidative Stress

2018 ◽  
Vol 73 (5) ◽  
pp. 289-293
Author(s):  
Evgeniya V. Shakhristova ◽  
Elena A. Stepovaya ◽  
Evgeniy V. Rudikov ◽  
Olga S. Sushitskaya ◽  
Daria O. Rodionova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Epithelial Cells ◽  
Breast Epithelial Cells ◽  
Redox Proteins ◽  
Cell Cycle Inhibitor ◽  
A Cell ◽  
Breast Epithelial

Background: Redox status imbalance against the backdrop of oxidative stress development underlies the pathogenesis of a whole range of diseases. Many intracellular proteins contain free thiol groups and undergo redox regulation which is one of the key processes in controlling cell proliferation. Thioredoxin and glutaredoxin are involved in maintaining intracellular redox homeostasis and act as candidates in regulating proliferation. This provides prospects for future development of methods for diagnosis and targeted therapy of socially sensitive diseases accompanied by oxidative stress. The aim of the study is to reveal the role of redox proteins in molecular mechanisms of regulating HBL-100 breast epithelial cell proliferation under the effect of roscovitine, a cell cycle inhibitor. Materials and methods: Two research groups were formed. They included HBL-100 human breast epithelial cells incubated in the presence and absence of 20 mcM roscovitine for 18 hours. The intracellular thioredoxin levels were determined using Western blot analysis with specific monoclonal antibodies. Distribution of the cells among cell cycle phases were evaluated by flow cytometry. The activity of glutathione reductase, glutathione peroxidase, and thioredoxin reductase were measured by spectrophotometry. Results: Under the effect of roscovitine in the HBL-100 cells, cell cycle arrest in the G2/М phases occurred and oxidative stress developed. In the meantime, the decrease in the thioredoxin and glutaredoxin concentrations was registered along with the change in the functional activity of glutathione-dependent enzymes. Conclusions: Application of roscovitine, a cell cycle inhibitor, allowed creating a model of oxidative stress in the breast epithelial cells against the backdrop of inhibited cell proliferation. We identified that thioredoxin and glutaredoxin contributed to impairment of cell cycle progression. It points at a possibility to regulate cell proliferation by modulating the functional features of cellular redox-dependent proteins in different pathologies accompanied by oxidative stress.

scholarly journals Nuclear pore density controls heterochromatin reorganization during senescence

2018 ◽  
Author(s):  
Charlene Boumendilrid ◽  
Priya Hari ◽  
Karl C. F. Olsen ◽  
Juan Carlos Acosta ◽  
Wendy A. Bickmore
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Tumour Progression ◽  
Nuclear Periphery ◽  
Nuclear Pore ◽  
Pore Density ◽  
Cycle Arrest ◽  
A Cell ◽  
Secretory Phenotype

AbstractOncogene induced senescence (OIS) is a cell cycle arrest program triggered by oncogenic signalling. An important characteristic of OIS is activation of the senescence associated secretory phenotype (SASP)1 which can reinforce cell cycle arrest, lead to paracrine senescence but also promote tumour progression2–4. Concomitant with cell cycle arrest and the SASP activation, OIS cells undergo a striking nuclear chromatin reorganization, with loss of heterochromatin from the nuclear periphery and the appearance of internal senescence-associated heterochromatin foci (SAHF)5. The mechanisms by which SAHF are formed, and their role in cell cycle arrest and expression of the SASP, remain poorly understood. Here we show that nuclear pore density increases during OIS and is responsible for SAHF formation. In particular, we show that the nucleoporin TPR is required for both SAHF formation and maintenance. The TPR-induced loss of SAHF does not affect cell cycle arrest but completely abrogates the SASP. Our results uncover a previously unknown role of nuclear pores in heterochromatin reorganization in mammalian nuclei and in senescence, which uncouples the cell cycle arrest from the SASP.

scholarly journals Role of Mis Localization of DNA Repair Factors in Cell Cycle Arrest

2019 ◽  
Vol 116 (3) ◽  
pp. 76a
Author(s):  
Manasvita Vashisth ◽  
Sangkyun Cho ◽  
Dennis Discher
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

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 The Anti-Tumor Activity of the NEDD8 Inhibitor Pevonedistat in Neuroblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6565
Author(s):  
Jennifer H. Foster ◽  
Eveline Barbieri ◽  
Linna Zhang ◽  
Kathleen A. Scorsone ◽  
Myrthala Moreno-Smith ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Wild Type ◽  
Tumor Weight ◽  
Cycle Arrest ◽  
P53 Status ◽  
Neuroblastoma Cell Lines ◽  
Anti Tumor Activity

Pevonedistat is a neddylation inhibitor that blocks proteasomal degradation of cullin–RING ligase (CRL) proteins involved in the degradation of short-lived regulatory proteins, including those involved with cell-cycle regulation. We determined the sensitivity and mechanism of action of pevonedistat cytotoxicity in neuroblastoma. Pevonedistat cytotoxicity was assessed using cell viability assays and apoptosis. We examined mechanisms of action using flow cytometry, bromodeoxyuridine (BrDU) and immunoblots. Orthotopic mouse xenografts of human neuroblastoma were generated to assess in vivo anti-tumor activity. Neuroblastoma cell lines were very sensitive to pevonedistat (IC50 136–400 nM). The mechanism of pevonedistat cytotoxicity depended on p53 status. Neuroblastoma cells with mutant (p53MUT) or reduced levels of wild-type p53 (p53si-p53) underwent G2-M cell-cycle arrest with rereplication, whereas p53 wild-type (p53WT) cell lines underwent G0-G1 cell-cycle arrest and apoptosis. In orthotopic neuroblastoma models, pevonedistat decreased tumor weight independent of p53 status. Control mice had an average tumor weight of 1.6 mg + 0.8 mg versus 0.5 mg + 0.4 mg (p < 0.05) in mice treated with pevonedistat. The mechanism of action of pevonedistat in neuroblastoma cell lines in vitro appears p53 dependent. However, in vivo studies using mouse neuroblastoma orthotopic models showed a significant decrease in tumor weight following pevonedistat treatment independent of the p53 status. Novel chemotherapy agents, such as the NEDD8-activating enzyme (NAE) inhibitor pevonedistat, deserve further study in the treatment of neuroblastoma.

scholarly journals Proteotoxic Stress Induces a Cell-Cycle Arrest by Stimulating Lon to Degrade the Replication Initiator DnaA

Cell ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 623-636 ◽  
Author(s):  
Kristina Jonas ◽  
Jing Liu ◽  
Peter Chien ◽  
Michael T. Laub
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Proteotoxic Stress ◽  
Cycle Arrest ◽  
A Cell ◽  
Replication Initiator

scholarly journals Cellular Senescence in Liver Disease and Regeneration

2021 ◽  
Author(s):  
Sofia Ferreira-Gonzalez ◽  
Daniel Rodrigo-Torres ◽  
Victoria L. Gadd ◽  
Stuart J. Forbes
Keyword(s):  
Cell Cycle ◽  
Liver Disease ◽  
Cell Cycle Arrest ◽  
Genomic Instability ◽  
Cellular Senescence ◽  
Cell Populations ◽  
Cycle Arrest ◽  
Relevant Role ◽  
Extent Of Damage

AbstractCellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanisms acting on the cell populations of the liver will be described including the role of markers to detect cellular senescence. Overall, this review intends to summarize the role of senescence in liver homeostasis, injury, disease, and regeneration.

The essential role of p21 in radiation-induced cell cycle arrest of vascular smooth muscle cell

2004 ◽  
Vol 37 (4) ◽  
pp. 871-880 ◽  
Author(s):  
Hyo-Soo Kim ◽  
Hyun-Jai Cho ◽  
Hyun-Ju Cho ◽  
Sun-Jung Park ◽  
Kyung-Woo Park ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Cell Cycle Arrest ◽  
Muscle Cell ◽  
Essential Role ◽  
Cycle Arrest ◽  
Radiation Induced

scholarly journals Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

2018 ◽  
Vol 51 (5) ◽  
pp. 2185-2197 ◽  
Author(s):  
Lili Men ◽  
Juan Sun ◽  
Decheng Ren
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Insulin Secretion ◽  
Cell Apoptosis ◽  
Β Cells ◽  
Β Cell ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Insulinoma Cells

Background/Aims: VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in β-cells, however, the role of VIMP in β-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and β-cell survival in MIN6 insulinoma cells. Methods: To determine the role of VIMP in β-cells, lentiviral VIMP shRNAs were used to knock down (KD) expression of VIMP in MIN6 cells. Cell death was quantified by propidium iodide (PI) staining followed by flow cytometric analyses using a FACS Caliber and FlowJo software. Cell apoptosis and proliferation were determined by TUNEL assay and Ki67 staining, respectively. Cell cycle was analyzed after PI staining. Results: The results show that 1) VIMP suppression induces β-cell apoptosis, which is associated with a decrease in Bcl-xL, and the β-cell apoptosis induced by VIMP suppression can be inhibited by overexpression of Bcl-xL; 2) VIMP knockdown (KD) decreases cell proliferation and G1 cell cycle arrest by accumulating p27 and decreasing E2F1; 3) VIMP KD suppresses unfolded protein response (UPR) activation by regulating the IRE1α and PERK pathways; 4) VIMP KD increases insulin secretion. Conclusion: These results suggest that VIMP may function as a novel regulator to modulate β-cell survival, proliferation, cell cycle, UPR and insulin secretion in MIN6 cells.

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