scholarly journals Human Speedy

2002 ◽  
Vol 157 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Lisa A. Porter ◽  
Ryan W. Dellinger ◽  
John A. Tynan ◽  
Elizabeth A. Barnes ◽  
Monica Kong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
S Phase ◽  
Cell Cycle Gene ◽  
Cell Cycle Protein ◽  
Cell Progression ◽  
A Cell ◽  
Immortalized Cell ◽  
Cycle Regulation

The decision for a cell to self-replicate requires passage from G1 to S phase of the cell cycle and initiation of another round of DNA replication. This commitment is a critical one that is tightly regulated by many parallel pathways. Significantly, these pathways converge to result in activation of the cyclin-dependent kinase, cdk2. It is, therefore, important to understand all the mechanisms regulating cdk2 to determine the molecular basis of cell progression. Here we report the identification and characterization of a novel cell cycle gene, designated Speedy (Spy1). Spy1 is 40% homologous to the Xenopus cell cycle gene, X-Spy1. Similar to its Xenopus counterpart, human Speedy is able to induce oocyte maturation, suggesting similar biological characteristics. Spy1 mRNA is expressed in several human tissues and immortalized cell lines and is only expressed during the G1/S phase of the cell cycle. Overexpression of Spy1 protein demonstrates that Spy1 is nuclear and results in enhanced cell proliferation. In addition, flow cytometry profiles of these cells demonstrate a reduction in G1 population. Changes in cell cycle regulation can be attributed to the ability of Spy1 to bind to and prematurely activate cdk2 independent of cyclin binding. We demonstrate that Spy1-enhanced cell proliferation is dependent on cdk2 activation. Furthermore, abrogation of Spy1 expression, through the use of siRNA, demonstrates that Spy1 is an essential component of cell proliferation pathways. Hence, human Speedy is a novel cell cycle protein capable of promoting cell proliferation through the premature activation of cdk2 at the G1/S phase transition.

scholarly journals Yeast cell cycle protein CDC48p shows full-length homology to the mammalian protein VCP and is a member of a protein family involved in secretion, peroxisome formation, and gene expression.

1991 ◽  
Vol 114 (3) ◽  
pp. 443-453 ◽  
Author(s):  
K U Fröhlich ◽  
H W Fries ◽  
M Rüdiger ◽  
R Erdmann ◽  
D Botstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Fusion Protein ◽  
Intracellular Transport ◽  
Consensus Sequence ◽  
Cell Cycle Gene ◽  
Cell Cycle Protein ◽  
A Cell ◽  
Yeast Mutants ◽  
Mammalian Protein

Yeast mutants of cell cycle gene cdc48-1 arrest as large budded cells with microtubules spreading aberrantly throughout the cytoplasm from a single spindle plaque. The gene was cloned and disruption proved it to be essential. The CDC48 sequence encodes a protein of 92 kD that has an internal duplication of 200 amino acids and includes a nucleotide binding consensus sequence. Vertebrate VCP has a 70% identity over the entire length of the protein. Yeast Sec18p and mammalian N-ethylmaleimide-sensitive fusion protein, which are involved in intracellular transport, yeast Pas1p, which is essential for peroxisome assembly, and mammalian TBP-1, which influences HIV gene expression, are 40% identical in the duplicated region. Antibodies against CDC48 recognize a yeast protein of apparently 115 kD and a mammalian protein of 100 kD. Both proteins are bound loosely to components of the microsomal fraction as described for Sec18p and N-ethylmaleimide-sensitive fusion protein. This similarity suggests that CDC48p participates in a cell cycle function related to that of N-ethylmaleimide-sensitive fusion protein/Sec18p in Golgi transport.

Cytological and microspectrophotometric analysis of mesodermalized explants of Triturus gastrula ectoderm

Development ◽  
1976 ◽  
Vol 36 (1) ◽  
pp. 55-66
Author(s):  
Shinichi Noda ◽  
Izumi Kawakami
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mitotic Index ◽  
Cell Number ◽  
S Phase ◽  
Abrupt Increase ◽  
A Cell ◽  
Triturus Pyrrhogaster ◽  
Rat Bone

Using isolated presumptive ectoderm of the newt (Triturus pyrrhogaster) embryos as a reactor and extract of rat bone marrow as a mesodermal inductor, changes of cell number and mitotic index of the reactor cells were studied. In early stages of cultivation the increase in cell number in the mesodermalized ectodermal piece was slower than in the non-mesodermalized epidermal piece; but after 24 h it showed abrupt increase and reached a cell population equal to that of the control at 48 h of cultivation. In the experimental series, the mitotic index was 0 at 4 h after the application of the inducing stimulus, but increased precipitously in the next 8 h and reached a level of 4·4% at 12 h and thereafter decreased gradually. The cell cycle stopped at the S phase and stayed in it for several hours after the application of inductor. A sudden fall in cell number, observed in the mesodermalized epidermal piece between the 4th and the 8th h after the application of inducing stimulus, seems to be attributable to cell death which was brought about by the inducing stimulus. In the histogenetic process phases of repression on mitosis by an inducing stimulus, cell proliferation and nonproliferation seem to succeed each other.

scholarly journals SNAPIN Regulates Cell Cycle Progression to Promote Pancreatic β Cell Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengxue Jiang ◽  
Zhijian Kuang ◽  
Yaohui He ◽  
Yin Cao ◽  
Tingyan Yu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Insulin Secretion ◽  
Cell Cycle Progression ◽  
Cell Number ◽  
S Phase ◽  
Mrna Levels ◽  
Β Cell ◽  
Cycle Regulation

In diabetes mellitus, death of β cell in the pancreas occurs throughout the development of the disease, with loss of insulin production. The maintenance of β cell number is essential to maintaining normoglycemia. SNAPIN has been found to regulate insulin secretion, but whether it induces β cell proliferation remains to be elucidated. This study aimed to explore the physiological roles of SNAPIN in β cell proliferation. SNAPIN expression increases with the age of mice and SNAPIN is down-regulated in diabetes. KEGG pathway and GO analysis showed that SNAPIN- interacting proteins were enriched in cell cycle regulation. B cell cycle was arrested in the S phase, and cell proliferation was inhibited after SNAPIN knockdown. The expression of CDK2, CDK4 and CCND1 proteins in the S phase of the cell cycle were reduced after SNAPIN knockdown, whereas they were increased after overexpression of SNAPIN. In addition, insulin protein and mRNA levels also increased or decreased after SNAPIN knockdown or overexpression, respectively. Conclusions: Our data indicate that SNAPIN mediates β cells proliferation and insulin secretion, and provide evidences that SNAPIN might be a pharmacotherapeutic target for diabetes mellitus.

scholarly journals Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Michela Levi ◽  
Roberta Salaroli ◽  
Federico Parenti ◽  
Raffaella De Maria ◽  
Augusta Zannoni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Tumour Cell ◽  
S Phase ◽  
Mammary Tumour ◽  
Cancer Resistance ◽  
Neoplastic Cells ◽  
Canine Mammary Tumour ◽  
Tumour Cell Lines

Abstract Background Doxorubicin (DOX) is widely used in both human and veterinary oncology although the onset of multidrug resistance (MDR) in neoplastic cells often leads to chemotherapy failure. Better understanding of the cellular mechanisms that circumvent chemotherapy efficacy is paramount. The aim of this study was to investigate the response of two canine mammary tumour cell lines, CIPp from a primary tumour and CIPm, from its lymph node metastasis, to exposure to EC50(20h) DOX at 12, 24 and 48 h of treatment. We assessed the uptake and subcellular distribution of DOX, the expression and function of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), two important MDR mediators. To better understand this phenomenon the effects of DOX on the cell cycle and Ki67 cell proliferation index and the expression of p53 and telomerase reverse transcriptase (TERT) were also evaluated by immunocytochemistry (ICC). Results Both cell lines were able to uptake DOX within the nucleus at 3 h treatment while at 48 h DOX was absent from the intracellular compartment (assessed by fluorescence microscope) in all the surviving cells. CIPm, originated from the metastatic tumour, were more efficient in extruding P-gp substrates. By ICC and qRT-PCR an overall increase in both P-gp and BCRP were observed at 48 h of EC50(20h) DOX treatment in both cell lines and were associated with a striking increase in the percentage of p53 and TERT expressing cells by ICC. The cell proliferation fraction was decreased at 48 h in both cell lines and cell cycle analysis showed a DOX-induced arrest in the S phase for CIPp, while CIPm had an increase in cellular death without arrest. Both cells lines were therefore composed by a fraction of cells sensible to DOX that underwent apoptosis/necrosis. Conclusions DOX administration results in interlinked modifications in the cellular population including a substantial effect on the cell cycle, in particular arrest in the S phase for CIPp and the selection of a subpopulation of neoplastic cells bearing MDR phenotype characterized by P-gp and BCRP expression, TERT activation, p53 accumulation and decrease in the proliferating fraction. Important information is given for understanding the dynamic and mechanisms of the onset of drug resistance in a neoplastic cell population.

scholarly journals JunB Breakdown in Mid-/Late G2 Is Required for Down-Regulation of Cyclin A2 Levels and Proper Mitosis

2008 ◽  
Vol 28 (12) ◽  
pp. 4173-4187 ◽  
Author(s):  
Rosa Farràs ◽  
Véronique Baldin ◽  
Sandra Gallach ◽  
Claire Acquaviva ◽  
Guillaume Bossis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Genetic Instability ◽  
S Phase ◽  
Subsequent Reduction ◽  
Suppressor Activity ◽  
Cell Synchronization ◽  
Tumor Suppressor Activity ◽  
A Cell ◽  
Cyclin A2

ABSTRACT JunB, a member of the AP-1 family of dimeric transcription factors, is best known as a cell proliferation inhibitor, a senescence inducer, and a tumor suppressor, although it also has been attributed a cell division-promoting activity. Its effects on the cell cycle have been studied mostly in G1 and S phases, whereas its role in G2 and M phases still is elusive. Using cell synchronization experiments, we show that JunB levels, which are high in S phase, drop during mid- to late G2 phase due to accelerated phosphorylation-dependent degradation by the proteasome. The forced expression of an ectopic JunB protein in late G2 phase indicates that JunB decay is necessary for the subsequent reduction of cyclin A2 levels in prometaphase, the latter event being essential for proper mitosis. Consistently, abnormal JunB expression in late G2 phase entails a variety of mitotic defects. As these aberrations may cause genetic instability, our findings contrast with the acknowledged tumor suppressor activity of JunB and reveal a mechanism by which the deregulation of JunB might contribute to tumorigenesis.

scholarly journals Posttranslational Phosphorylation and Ubiquitination of the Saccharomyces cerevisiae Poly(A) Polymerase at the S/G2 Stage of the Cell Cycle

2000 ◽  
Vol 20 (8) ◽  
pp. 2794-2802 ◽  
Author(s):  
Neptune Mizrahi ◽  
Claire Moore
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Sorting ◽  
S Phase ◽  
Phase Arrest ◽  
Phosphatase Treatment ◽  
M Phase ◽  
64 Kda Protein ◽  
Mitotic Phosphorylation ◽  
Cycle Regulation

ABSTRACT The poly(A) polymerase of the budding yeast Saccharomyces cerevisiae (Pap1) is a 64-kDa protein essential for the maturation of mRNA. We have found that a modified Pap1 of 90 kDa transiently appears in cells after release from α-factor-induced G1 arrest or from a hydroxyurea-induced S-phase arrest. While a small amount of modification occurs in hydroxyurea-arrested cells, fluorescence-activated cell sorting analysis and microscopic examination of bud formation indicate that the majority of modified enzyme is found at late S/G2 and disappears by the time cells have reached M phase. The reduction of the 90-kDa product upon phosphatase treatment indicates that the altered mobility is due to phosphorylation. A preparation containing primarily the phosphorylated Pap1 has no poly(A) addition activity, but this activity is restored by phosphatase treatment. A portion of Pap1 is also polyubiquitinated concurrent with phosphorylation. However, the bulk of the 64-kDa Pap1 is a stable protein with a half-life of 14 h. The timing, nature, and extent of Pap1 modification in comparison to the mitotic phosphorylation of mammalian poly(A) polymerase suggest an intriguing difference in the cell cycle regulation of this enzyme in yeast and mammalian systems.

scholarly journals Circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene

2020 ◽  
Author(s):  
Xinhua Qu ◽  
Liumei Zhu ◽  
Linlin Song ◽  
Shaohua Liu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Regulatory Network ◽  
Inhibitory Effect ◽  
Cervical Carcinogenesis ◽  
Activation Assay ◽  
Cell Cycle Related Gene ◽  
Rna Immunoprecipitation ◽  
A Cell ◽  
Brdu Assay

Abstract Background: Cervical cancer (CC) is a highly malignant tumor. Evolving researches on CC have unveiled a concept that circRNA exerts important roles in CC progression. In this study, we mainly explored the role of a novel circRNA, circ_0084927, and its regulatory network in the development of CC.Methods: qRT-PCR was applied to evaluate the expression of circ_0084927, miR-1179 and CDK2 mRNA in CC tissues and cells. Dual-luciferase reporting experiments and RNA immunoprecipitation (RIP) assay were conducted to validate the target relationship of miR-1179 with circ_0084927 and CDK2 mRNA. CCK-8 and BrdU assay was used to evaluate CC cell proliferation. The adhesion and apoptosis phenotypes of CC cells were measured by cell-matrix adhesion and caspase 3 activation assay. Flow cytometry was employed to detect CC cell cycle.Results: Our results indicated that circ_0084927 was up-regulated in CC tissues and cells, and circ_0084927 silence inhibited CC cell proliferation and adhesion, while facilitating apoptosis as well as triggering cell cycle arrest. On the other hand, miR-1179 down-regulation appeared in CC tissues. Additionally, circ_0084927 abolished miR-1179’s inhibitory effects on cell proliferation and adhesion. Our study showed that CDK2 was up-regulated in CC tissues and played a cancer-promoting role. Furthermore, miR-1179 directly targeted CDK2, thereby inhibiting CDK2’s promotion on the malignant phenotypes of CC cells. circ_0084927 revoked the inhibitory effect of miR-1179 on CDK2 by sponging miR-1179.Conclusion: Circ_0084927 promoted cervical carcinogenesis by sequestering miR-1179 that directly targeted CDK2. Our results shed light on the circ_0084927/miR-1179/CDK2 regulatory network that strengthened CC aggressiveness, providing novel candidate targets for CC treatment.

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