scholarly journals The Less Known Cyclins—Uncovered

2021 ◽  
Vol 11 (5) ◽  
pp. 2320
Author(s):  
Agnieszka Żuryń ◽  
Aleksandra Opacka ◽  
Adrian Krajewski ◽  
Wioletta Zielińska ◽  
Alina Grzanka
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Differentiation ◽  
Cancer Cells ◽  
Present Report ◽  
Life Stage ◽  
Cyclin Dependent Kinases ◽  
Current State ◽  
Different Types ◽  
A Cell

Cyclins belong to a group of proteins that are cyclically produced and destructed in a cell. Cyclins are a family of proteins that are a key component of the cell cycle regulating system, which level of expression depends on the phase of the cycle. Cyclins regulate the activity of cyclin-dependent kinases (Cdk), thanks to which they influence the length of individual phases of the cell cycle and also determine whether the cell can enter the next life stage. Proper expression of cyclins plays an important role in processes such as proliferation, transcription, DNA repair and cell differentiation. However, dysregulation of their expression is one of the most important disorders leading to the development of different types of cancer, which suggests that cyclins can be defined as a prognostic marker. Currently, we may distinguish >10 members of the cyclins family participating in the division of human cells. The group of less known cyclins includes C, F, G, H, I, J, K, L, M, O, T and Y cyclins. The present report demonstrates the current state of knowledge considering less known cyclins and their role in normal and cancer cells.

scholarly journals Wild-Type Tumor Repressor Protein 53 (TRP53) Promotes Ovarian Cancer Cell Survival

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1638-1648 ◽  
Author(s):  
Lisa K. Mullany ◽  
Zhilin Liu ◽  
Erin R. King ◽  
Kwong-Kwok Wong ◽  
JoAnne S. Richards
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Ovarian Cancer ◽  
Dna Repair ◽  
Cell Survival ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Low Grade ◽  
Wild Type ◽  
Repressor Protein

Loss of Pten in the KrasG12D;Amhr2-Cre mutant mice leads to the transformation of ovarian surface epithelial (OSE) cells and rapid development of low-grade, invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express elevated levels of wild-type tumor repressor protein 53 (TRP53). To test the functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene yielding Pten;Kras(Trp53−) mice. By comparing morphology and gene expression profiles in the Trp53+ and Trp53− OSE cells from these mice, we document that wild-type TRP53 acts as a major promoter of OSE cell survival and differentiation: cells lacking Trp53 are transformed yet are less adherent, migratory, and invasive and exhibit a gene expression profile more like normal OSE cells. These results provide a new paradigm: wild-type TRP53 does not preferentially induce apoptotic or senescent related genes in the Pten;Kras(Trp53+) cancer cells but rather increases genes regulating DNA repair, cell cycle progression, and proliferation and decreases putative tumor suppressor genes. However, if TRP53 activity is forced higher by exposure to nutlin-3a (a mouse double minute-2 antagonist), TRP53 suppresses DNA repair genes and induces the expression of genes that control cell cycle arrest and apoptosis. Thus, in the Pten;Kras(Trp53+) mutant mouse OSE cells and likely in human TP53+ low-grade ovarian cancer cells, wild-type TRP53 controls global molecular changes that are dependent on its activation status. These results suggest that activation of TP53 may provide a promising new therapy for managing low-grade ovarian cancer and other cancers in humans in which wild-type TP53 is expressed.

scholarly journals A cell cycle-regulated inhibitor of cyclin-dependent kinases.

1994 ◽  
Vol 91 (12) ◽  
pp. 5291-5295 ◽  
Author(s):  
L. Hengst ◽  
V. Dulic ◽  
J. M. Slingerland ◽  
E. Lees ◽  
S. I. Reed
Keyword(s):  
Cell Cycle ◽  
Cyclin Dependent Kinases ◽  
A Cell

Cyclin Dependent Kinases and Regulation of the Fission Yeast Cell Cycle

1999 ◽  
Vol 380 (7-8) ◽  
pp. 729-733 ◽  
Author(s):  
P. Nurse
Keyword(s):  
Cell Cycle ◽  
Yeast Cell ◽  
Fission Yeast ◽  
S Phase ◽  
Yeast Cell Cycle ◽  
Cyclin Dependent Kinases ◽  
Fission Yeast Cell ◽  
Nutritional Deprivation ◽  
Orderly Fashion ◽  
A Cell

AbstractThe cyclin dependent kinases (CDKs), formed by complexes between Cdc2p and the B-cyclins Cig2p and Cdc13p, have a central role in regulating the fission yeast cell cycle and maintaining genomic stability. The CDK Cig2p/Cdc2p controls the onset of S-phase and the CDK Cdc13p/Cdc2p controls the onset of mitosis and ensures that there is only one S-phase in each cell. Cdc13p/Cdc2p can replace Cig2p/Cdc2p for the onset of S-phase, suggesting that the increasing activity of a single CDK during the cell cycle is sufficient to drive a cell in an orderly fashion into S-phase and into mitosis. If S-phase is incomplete, then inhibition of Cdc13p/Cdc2p prevents cells with unreplicated DNA from undergoing a catastrophic entry into mitosis. Control of CDK activity is also important to allow cells to exit the cell cycle and accumulate in G1 in response to nutritional deprivation and the presence of pheromone.

scholarly journals A Cell Cycle-Dependent Regulatory Circuit Composed of 53BP1-RIF1 and BRCA1-CtIP Controls DNA Repair Pathway Choice

2013 ◽  
Vol 49 (5) ◽  
pp. 872-883 ◽  
Author(s):  
Cristina Escribano-Díaz ◽  
Alexandre Orthwein ◽  
Amélie Fradet-Turcotte ◽  
Mengtan Xing ◽  
Jordan T.F. Young ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Repair Pathway ◽  
Regulatory Circuit ◽  
A Cell ◽  
Pathway Choice ◽  
Cycle Dependent

scholarly journals p27Kip1 induces an accumulation of the repressor complexes of E2F and inhibits expression of the E2F-regulated genes.

1997 ◽  
Vol 8 (9) ◽  
pp. 1815-1827 ◽  
Author(s):  
P Shiyanov ◽  
S Hayes ◽  
N Chen ◽  
D G Pestov ◽  
L F Lau ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Binding Sites ◽  
Culture Medium ◽  
Cyclin E ◽  
Cyclin A ◽  
Cyclin Dependent Kinase ◽  
Binding Motifs ◽  
Cyclin Dependent Kinases ◽  
Cell Cycle Inhibition ◽  
A Cell

p27Kip1 is an inhibitor of the cyclin-dependent kinases and it plays an inhibitory role in the progression of cell cycle through G1 phase. To investigate the mechanism of cell cycle inhibition by p27Kip1, we constructed a cell line that inducibly expresses p27Kip1 upon addition of isopropyl-1-thio-beta-D-galactopyranoside in the culture medium. Isopropyl-1-thio-beta-D-galactopyranoside-induced expression of p27Kip1 in these cells causes a specific reduction in the expression of the E2F-regulated genes such as cyclin E, cyclin A, and dihydrofolate reductase. The reduction in the expression of these genes correlates with the p27Kip1-induced accumulation of the repressor complexes of the E2F family of factors (E2Fs). Our previous studies indicated that p21WAF1 could disrupt the interaction between cyclin/cyclin-dependent kinase 2 (cdk2) and the E2F repressor complexes E2F-p130 and E2F-p107. We show that p27Kip1, like p21WAF1, disrupts cyclin/cdk2-containing complexes of E2F-p130 leading to the accumulation of the E2F-p130 complexes, which is found in growth-arrested cells. In transient transfection assays, expression of p27Kip1 specifically inhibits transcription of a promoter containing E2F-binding sites. Mutants of p27Kip1 harboring changes in the cyclin- and cdk2-binding motifs are deficient in inhibiting transcription from the E2F sites containing reporter gene. Moreover, these mutants of p27Kip1 are also impaired in disrupting the interaction between cyclin/cdk2 and the repressor complexes of E2Fs. Taken together, these observations suggest that p27Kip1 reduces expression of the E2F-regulated genes by generating repressor complexes of E2Fs. Furthermore, the results also demonstrate that p27Kip1 inhibits expression of cyclin A and cyclin E, which are critical for progression through the G1-S phases.

scholarly journals NU7441 Enhances the Radiosensitivity of Liver Cancer Cells

2016 ◽  
Vol 38 (5) ◽  
pp. 1897-1905 ◽  
Author(s):  
Chuanjie Yang ◽  
Quanxu Wang ◽  
Xiaodan Liu ◽  
Xiulian Cheng ◽  
Xiaoyu Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Liver Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Specific Inhibitor ◽  
Cell Counting ◽  
Liver Cancer Cells

Objective: Radiation therapy, one of the major treatments for liver cancer, causes DNA damage and cell death. Since the liver cancer cells have a strong capacity to repair irradiative injury, new medicines to enhance this treatment are urgently required. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-dependent protein kinase (DNA-PK) in radiosensitization of hepatocellular carcinoma HepG2 cells. Methods: Cell Counting Kit-8 (CCK-8) was first used to evaluate the proliferation of HepG2 cells under NU7441 treatment. SDS-PAGE and Western blot were then performed to study the protein expression leading to the DNA damage repair. Further, neutral single cell gel electrophoresis and immunofluorescence assay were carried out to assess DNA repair. Finally, flow cytometry was implemented to examine the changes in cell cycle. Results: NU7441 reduced the CCK-8 counts in the HepG2 culture, further enhanced 60Coγ radiation injury to HepG2 cells, which was manifested by decreasing the DNA-PKcs (S2056) protein expression, increasing γH2AX foci number, prolonging the tail moment of the comet cells, and inducing cell cycle arrest at G2/M phase. Conclusion: NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer.

scholarly journals Cyclin-dependent Kinases Phosphorylate p73 at Threonine 86 in a Cell Cycle-dependent Manner and Negatively Regulate p73

2003 ◽  
Vol 278 (30) ◽  
pp. 27421-27431 ◽  
Author(s):  
Christian Gaiddon ◽  
Maria Lokshin ◽  
Isabelle Gross ◽  
Danielle Levasseur ◽  
Yoichi Taya ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dependent Manner ◽  
Cyclin Dependent Kinases ◽  
A Cell ◽  
Cycle Dependent

scholarly journals The oscillation of mitotic kinase governs cell cycle latches

2021 ◽  
Author(s):  
Bela Novak ◽  
John J Tyson
Keyword(s):  
Cell Cycle ◽  
Negative Feedback ◽  
Molecular Switches ◽  
Feedback Loops ◽  
Yeast Cells ◽  
Cyclin Dependent Kinases ◽  
Mitotic Kinase ◽  
Daughter Cells ◽  
Negative Feedback Loops ◽  
A Cell

SummaryIn order to transmit a eukaryotic cell’s genome accurately from mother cell to daughter cells, it is essential that the basic events of the cell division cycle (DNA synthesis and mitosis) occur once and only once per cycle, i.e., that a cell progresses irreversibly from G1 to S to G2 to M and back to G1. Irreversible progression through the cell cycle is assured by a sequence of ‘latching’ molecular switches, based on molecular interactions among cyclin-dependent kinases and their auxiliary partners. Positive feedback loops (++ or −−) create bistable switches with latching properties, and negative feedback loops drive progression from one stage to the next. In budding yeast (Saccharomyces cerevisiae) these events are coordinated by double-negative feedback loops between Clb-dependent kinases (Clb1-6) and their antagonists (APC:Cdh1 and Sic1). If the coordinating signal is compromised, either by deletion of Clb1-5 proteins or expression of non-degradable Clb2, then irreversibility is lost and yeast cells exhibit multiple rounds of DNA replication or mitotic exit events (Cdc14 endocycles). Using mathematical modelling of a stripped-down control network, we show how endocycles arise because the switches fail to latch, and the gates swing back and forth by the action of the negative feedback loops.

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