Modulation of the nuclear antigen p105 as a function of cell-cycle progression

1987 ◽  
Vol 130 (3) ◽  
pp. 336-343 ◽  
Author(s):  
Charles V. Clevenger ◽  
Alan L. Epstein ◽  
Kenneth D. Bauer
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Cycle Progression

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 CREB Regulates Cell Cycle Progression through RFC3-PCNA Axis in Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 881-881
Author(s):  
Hee-Don Chae ◽  
Bryan Mitton ◽  
Kathleen Sakamoto
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Promoter Region ◽  
Myeloid Leukemia ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Conflicts Of Interest ◽  
Nuclear Antigen ◽  
Cycle Progression ◽  
Acute Myeloid

Abstract CREB (cAMP Response Element Binding protein) is a transcription factor overexpressed in normal and neoplastic myelopoiesis and regulates cell cycle progression, although its oncogenic mechanism has not been well characterized. Replication Factor C3 (RFC3), a 38 kDa subunit of the RFC complex, is required for chromatin loading of proliferating cell nuclear antigen (PCNA) which is a sliding clamp platform for recruiting numerous proteins in DNA replication and repair processes. CREB1 expression was coupled with RFC3 expression during the G1/S progression in the KG-1 acute myeloid leukemia (AML) cell line, suggesting that RFC3 and CREB1 might be target genes of E2F, a key transcriptional regulator of the G1/S progression. Though there were two potential E2F binding sites in the RFC3 promoter region, chromatin immunoprecipitation assays provided no evidence for E2F1 binding to the RFC3 promoter, whereas E2F1 could directly act on the CREB1 expression. Treatment with the cyclin-dependent kinase (CDK) inhibitor AT7519 decreased expression of CREB1 and RFC3 as well as well-known E2F target genes such as CCNE1, CCNA2 and CCNB1 in KG-1 cells. These results indicate that CREB1 overexpression, a potentially important prognostic marker in leukemia patients, may be associated with dysregulated CDK-E2F activity in leukemia. There was also a direct correlation between the expression of RFC3 and CREB1 in human AML cell lines as well as in AML cells from patients. CREB interacted directly with the CRE site in RFC3 promoter region. CREB knockdown primarily inhibited G1/S cell cycle transition, decreasing expression of RFC3 as well as PCNA loading onto chromatin. Exogenous expression of RFC3 was sufficient to rescue the impaired G1/S progression and PCNA chromatin loading [Chromatin-bound PCNA-positive cells (%), control vs. CREB-knockdown vs. CREB-knockdown with RFC3 overexpression, 8h after release from mitotic arrest: 66.87 +/– 0.90 vs. 24.77 +/– 0.99 vs. 79.17 +/– 0.12, n=3, p< 0.01, mean +/– SEM] caused by CREB knockdown. Taken together, our results suggest that RFC3 may play a role in neoplastic myelopoiesis by promoting the G1/S progression, and its expression is regulated by CREB. These data provide new insight into CREB-driven regulation of the cell cycle in AML cells, and may contribute to leukemogenesis associated with CREB overexpression. Disclosures No relevant conflicts of interest to declare.

scholarly journals Extracellular Signal-Regulated Kinase 2-Dependent Phosphorylation Induces Cytoplasmic Localization and Degradation of p21Cip1

2009 ◽  
Vol 29 (12) ◽  
pp. 3379-3389 ◽  
Author(s):  
Chae Young Hwang ◽  
Cheolju Lee ◽  
Ki-Sun Kwon
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Inhibitory Protein ◽  
Cycle Progression ◽  
Double Mutation ◽  
Extracellular Signal Regulated Kinase ◽  
Epidermal Growth Factor Treatment ◽  
Extracellular Signal

ABSTRACT p21Cip1 is an inhibitor of cell cycle progression that promotes G1-phase arrest by direct binding to cyclin-dependent kinase and proliferating cell nuclear antigen. Here we demonstrate that mitogenic stimuli, such as epidermal growth factor treatment and oncogenic Ras transformation, induce p21Cip1 downregulation at the posttranslational level. This downregulation requires the sustained activation of extracellular signal-regulated kinase 2 (ERK2), which directly interacts with and phosphorylates p21Cip1, promoting p21Cip1 nucleocytoplasmic translocation and ubiquitin-dependent degradation, thereby resulting in cell cycle progression. ERK1 is not likely involved in this process. Phosphopeptide analysis of in vitro ERK2-phosphorylated p21Cip1 revealed two phosphorylation sites, Thr57 and Ser130. Double mutation of these sites abolished ERK2-mediated p21Cip1 translocation and degradation, thereby impairing ERK2-dependent cell cycle progression at the G1/S transition. These results indicate that ERK2 activation transduces mitogenic signals, at least in part, by downregulating the cell cycle inhibitory protein p21Cip1.

Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4097-4103 ◽  
Author(s):  
Yasuhito Ide ◽  
Daisuke Tsuchimoto ◽  
Yohei Tominaga ◽  
Manabu Nakashima ◽  
Takeshi Watanabe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Proliferating Cell Nuclear Antigen ◽  
Cell Cycle Progression ◽  
Immunoglobulin M ◽  
Nuclear Antigen ◽  
Wild Type ◽  
Cycle Progression ◽  
Class Switch ◽  
M Phase ◽  
Proliferating Cell

Abstract APEX2/APE2 is a secondary mammalian apurinic/apyrimidinic endonuclease that associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. To determine the biologic significance of APEX2, we established APEX2-null mice. These mice were about 80% the size of their wild-type littermates and exhibited a moderate dyshematopoiesis and a relatively severe defect in lymphopoiesis. A significant accumulation of both thymocytes and mitogen-stimulated splenocytes in G2/M phase was seen in APEX2-null mice compared with the wild type, indicating that APEX2 is required for proper cell cycle progression of proliferating lymphocytes. Although APEX2-null mice exhibited an attenuated immune response against ovalbumin in comparison with wild-type mice, they produced both antiovalbumin immunoglobulin M (IgM) and IgG, indicating that class switch recombination can occur even in the absence of APEX2. (Blood. 2004;104: 4097-4103)

scholarly journals Epstein-Barr Virus Nuclear Antigen 3C Regulates Cyclin A/p27 Complexes and Enhances Cyclin A-Dependent Kinase Activity

2004 ◽  
Vol 78 (4) ◽  
pp. 1981-1991 ◽  
Author(s):  
Jason S. Knight ◽  
Erle S. Robertson
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Cell Transformation ◽  
Cyclin A ◽  
Nuclear Antigen ◽  
Cycle Progression ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is essential for primary B-cell transformation. In this report we show that cyclin A, an activator of S phase progression, bound tightly to EBNA3C. EBNA3C interacted with cyclin A in vitro and associated with cyclin A complexes in EBV-transformed lymphoblastoid cell lines. Importantly, EBNA3C stimulated cyclin A-dependent kinase activity and rescued p27-mediated inhibition of cyclin A/Cdk2 kinase activity by decreasing the molecular association between cyclin A and p27 in cells. Additionally, phosphorylation of the retinoblastoma protein, a major regulator of cell cycle progression, was enhanced both in vitro and in vivo in the presence of EBNA3C. Cyclin A interacted with a region of the carboxy terminus of EBNA3C, shown to be important both for stimulation of cyclin A-dependent kinase activity and for cell cycle progression. This provides the first evidence of an essential EBV latent antigen's directly targeting a cell cycle regulatory protein and suggests a novel mechanism by which EBV deregulates the mammalian cell cycle, which is of critical importance in B-cell transformation.

scholarly journals Epstein-Barr Virus Nuclear Antigen 3C Facilitates Cell Proliferation by Regulating Cyclin D2

2018 ◽  
Vol 92 (18) ◽  
Author(s):  
Yonggang Pei ◽  
Rajnish Kumar Singh ◽  
Sanket Kumar Shukla ◽  
Fengchao Lang ◽  
Shengwei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Epstein Barr Virus ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Cyclin D2 ◽  
Cycle Progression ◽  
Barr Virus ◽  
Epstein Barr ◽  
Related Proteins

ABSTRACTCell cycle regulation is one of the hallmarks of virus-mediated oncogenesis. Epstein-Barr virus (EBV)-induced lymphomas express a repertoire of essential viral latent proteins that regulate expression of cell cycle-related proteins to dysregulate this process, thereby facilitating the proliferation of infected cells. We now demonstrate that the essential EBV latent protein 3C (EBNA3C) stabilizes cyclin D2 to regulate cell cycle progression. More specifically, EBNA3C directly binds to cyclin D2 and they colocalize together in nuclear compartments. We show that EBNA3C regulates the promoter of cyclin D2 through cooperation with master transcription factor Bcl6 and enhances its stability by inhibiting its ubiquitin-dependent degradation. EBNA3C also promoted cell proliferation in the presence of cyclin D2, suggesting that cyclin D2 contributes to EBNA3C-mediated cell cycle progression. These results provide new clues as to the role of this essential viral latent protein and its ability to regulate expression of cellular factors, which drives the oncogenic process.IMPORTANCEEpstein-Barr virus (EBV) is the first identified human tumor virus and is associated with a range of human cancers. During EBV-induced lymphomas, the essential viral latent proteins modify the expression of cell cycle-related proteins to disturb the cell cycle process, thereby facilitating the proliferative process. The essential EBV nuclear antigen 3C (EBNA3C) plays an important role in EBV-mediated B-cell transformation. Here we show that EBNA3C stabilizes cyclin D2 to regulate cell cycle progression. More specifically, EBNA3C directly binds to cyclin D2, and they colocalize together in nuclear compartments. EBNA3C enhances cyclin D2 stability by inhibiting its ubiquitin-dependent degradation and significantly promotes cell proliferation in the presence of cyclin D2. Our results provide novel insights into the function of EBNA3C on cell progression by regulating the cyclin D2 protein and raise the possibility of the development of new anticancer therapies against EBV-associated cancers.

scholarly journals Effect of Surface Coating of Gold Nanoparticles on Cytotoxicity and Cell Cycle Progression

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1063 ◽  
Author(s):  
Qian Li ◽  
Chun Huang ◽  
Liwei Liu ◽  
Rui Hu ◽  
Junle Qu
Keyword(s):  
Cell Cycle ◽  
Gold Nanoparticles ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Biocompatible Polymers ◽  
G1 Arrest ◽  
Cycle Progression ◽  
Microtubule Stabilization ◽  
Lysosomal Accumulation ◽  
Proliferating Cell

Gold nanoparticles (GNPs) are usually wrapped with biocompatible polymers in biomedical field, however, the effect of biocompatible polymers of gold nanoparticles on cellular responses are still not fully understood. In this study, GNPs with/without polymer wrapping were used as model probes for the investigation of cytotoxicity and cell cycle progression. Our results show that the bovine serum albumin (BSA) coated GNPs (BSA-GNPs) had been transported into lysosomes after endocytosis. The lysosomal accumulation had then led to increased binding between kinesin 5 and microtubules, enhanced microtubule stabilization, and eventually induced G2/M arrest through the regulation of cadherin 1. In contrast, the bare GNPs experienced lysosomal escape, resulting in microtubule damage and G0/G1 arrest through the regulation of proliferating cell nuclear antigen. Overall, our findings showed that both naked and BSA wrapped gold nanoparticles had cytotoxicity, however, they affected cell proliferation via different pathways. This will greatly help us to regulate cell responses for different biomedical applications.

Overexpression of E2F-1 leads to cytokine-independent proliferation and survival in the hematopoietic cell line BaF-B03

Blood ◽  
2001 ◽  
Vol 97 (1) ◽  
pp. 227-234 ◽  
Author(s):  
Salvador Gala ◽  
Alexandra Marreiros ◽  
Graeme J. Stewart ◽  
Peter Williamson
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Cell Cycle Progression ◽  
Constitutive Expression ◽  
Cell Types ◽  
Cyclin B1 ◽  
Nuclear Antigen ◽  
Cycle Progression ◽  
Cytokine Stimulation ◽  
Cycle Dependent

Abstract Cytokine receptors activate signals that regulate the transcription factor E2F-1, which then coordinates the expression of genes essential for DNA synthesis and cell cycle progression. Overexpression of E2F-1 most often induces S-phase entry followed by apoptosis, but in some cell types it leads to continuous proliferation and transformation. Here, it is shown that constitutive expression of E2F-1 promotes cytokine-independent proliferation in the murine pro-B cell line BaF-B03. There was no enhancement of apoptosis following cytokine withdrawal in these cells, despite the presence of intact p53-dependent apoptotic pathways. Notwithstanding the continuous presence of E2F-1, the cell cycle–dependent expression of cyclin A, cyclin B1, cyclin D1, cyclin E, and proliferating-cell nuclear antigen was restored with a pattern equivalent to that associated with cytokine stimulation. These findings provide evidence that, in the absence of cytokine, constitutive expression of E2F-1 can promote cell cycle progression and prevent apoptosis.

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