scholarly journals [Corrigendum] c‑Myc regulates the CDK1/cyclin B1 dependent‑G2/M cell cycle progression by histone H4 acetylation in Raji cells

2019 ◽  
Author(s):  
Yan Yang ◽  
Kai Xue ◽  
Zhi Li ◽  
Wei Zheng ◽  
Weijie Dong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Histone H4 ◽  
M Cell ◽  
Cycle Progression ◽  
Raji Cells ◽  
Histone H4 Acetylation

scholarly journals Activation of the G2/M-Specific Gene CLB2 Requires Multiple Cell Cycle Signals

2007 ◽  
Vol 27 (23) ◽  
pp. 8364-8373 ◽  
Author(s):  
J. Veis ◽  
H. Klug ◽  
M. Koranda ◽  
G. Ammerer
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Specific Gene ◽  
Histone H4 ◽  
Cycle Progression ◽  
Histone H4 Acetylation ◽  
Multiple Cell

ABSTRACT In budding yeast (Saccharomyces cerevisiae), the periodic expression of the G2/M-specific gene CLB2 depends on a DNA binding complex that mediates its repression during G1 and activation from the S phase to the exit of mitosis. The switch from low to high expression levels depends on the transcriptional activator Ndd1. We show that the inactivation of the Sin3 histone deacetylase complex bypasses the essential role of Ndd1 in cell cycle progression. Sin3 and its catalytic subunit Rpd3 associate with the CLB2 promoter during the G1 phase of the cell cycle. Both proteins dissociate from the promoter at the onset of the S phase and reassociate during G2 phase. Sin3 removal coincides with a transient increase in histone H4 acetylation followed by the expulsion of at least one nucleosome from the promoter region. Whereas the first step depends on Cdc28/Cln1 activity, Ndd1 function is required for the second step. Since the removal of Sin3 is independent of Ndd1 recruitment and Cdc28/Clb activity it represents a unique regulatory step which is distinct from transcriptional activation.

scholarly journals Regulation of the G2–M cell cycle progression by the ERK5–NFκB signaling pathway

2007 ◽  
Vol 177 (2) ◽  
pp. 253-264 ◽  
Author(s):  
Kelly Cude ◽  
Yupeng Wang ◽  
Hyun-Jung Choi ◽  
Shih-Ling Hsuan ◽  
Honglai Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cancer Biology ◽  
Cell Cycle Progression ◽  
Nuclear Factor Κb ◽  
Cyclin B1 ◽  
M Cell ◽  
Cycle Progression ◽  
Mitotic Entry ◽  
Ribosomal S6 Kinase

Elucidation of mechanisms regulating cell cycle progression is of fundamental importance for cell and cancer biology. Although several genes and signaling pathways are implicated in G1–S regulation, less is known regarding the mechanisms controlling cell cycle progression through G2 and M phases. We report that extracellular signal–regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinases, is activated at G2–M and required for timely mitotic entry. Stimulation of ERK5 activated nuclear factor κB (NFκB) through ribosomal S6 kinase 2 (RSK2)-mediated phosphorylation and degradation of IκB. Furthermore, selective inhibition of NFκB at G2–M phases substantially delayed mitotic entry and inhibited transcription of G2–M–specific genes, including cyclin B1, cyclin B2, Plk-1, and cdc25B. Moreover, inhibition of NFκB at G2–M diminished mitosis induced by constitutive activation of ERK5, providing a direct link between ERK5, NFκB, and regulation of G2–M progression. We conclude that a novel ERK5–NFκB signaling pathway plays a key role in regulation of the G2–M progression.

scholarly journals Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes

2021 ◽  
Vol 43 (3) ◽  
pp. 1436-1450
Author(s):  
Leonardo Vinícius Monteiro de Assis ◽  
Maria Nathália Moraes ◽  
Davi Mendes ◽  
Matheus Molina Silva ◽  
Carlos Frederico Martins Menck ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Population Analysis ◽  
Cell Populations ◽  
Specific Cell ◽  
Significant Modification ◽  
M Cell ◽  
Cycle Progression ◽  
Gene And Protein Expression ◽  
Independent Functions

Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine Opn4KO melanocytes displayed a faster proliferation rate compared to Opn4WT melanocytes. Cell cycle population analysis demonstrated that OPN4KO melanocytes exhibited a faster cell cycle progression with reduced G0–G1, and highly increased S and slightly increased G2/M cell populations compared to the Opn4WT counterparts. Expression of specific cell cycle-related genes in Opn4KO melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in Opn4KO melanocytes compared to Opn4WT cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in Opn4KO melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.

scholarly journals Akt/Protein Kinase B-Dependent Phosphorylation and Inactivation of WEE1Hu Promote Cell Cycle Progression at G2/M Transition

2005 ◽  
Vol 25 (13) ◽  
pp. 5725-5737 ◽  
Author(s):  
Kazuhiro Katayama ◽  
Naoya Fujita ◽  
Takashi Tsuruo
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Phosphorylation Site ◽  
Cytoplasmic Localization ◽  
M Cell ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
M Phase ◽  
Promote Cell Cycle Progression

ABSTRACT The serine/threonine kinase Akt is known to promote cell growth by regulating the cell cycle in G1 phase through activation of cyclin/Cdk kinases and inactivation of Cdk inhibitors. However, how the G2/M phase is regulated by Akt remains unclear. Here, we show that Akt counteracts the function of WEE1Hu. Inactivation of Akt by chemotherapeutic drugs or the phosphatidylinositide-3-OH kinase inhibitor LY294002 induced G2/M arrest together with the inhibitory phosphorylation of Cdc2. Because the increased Cdc2 phosphorylation was completely suppressed by wee1hu gene silencing, WEE1Hu was associated with G2/M arrest induced by Akt inactivation. Further analyses revealed that Akt directly bound to and phosphorylated WEE1Hu during the S to G2 phase. Serine-642 was identified as an Akt-dependent phosphorylation site. WEE1Hu kinase activity was not affected by serine-642 phosphorylation. We revealed that serine-642 phosphorylation promoted cytoplasmic localization of WEE1Hu. The nuclear-to-cytoplasmic translocation was mediated by phosphorylation-dependent WEE1Hu binding to 14-3-3θ but not 14-3-3β or -σ. These results indicate that Akt promotes G2/M cell cycle progression by inducing phosphorylation-dependent 14-3-3θ binding and cytoplasmic localization of WEE1Hu.

scholarly journals Distinct Cell Cycle Timing Requirements for Extracellular Signal-Regulated Kinase and Phosphoinositide 3-Kinase Signaling Pathways in Somatic Cell Mitosis

2002 ◽  
Vol 22 (20) ◽  
pp. 7226-7241 ◽  
Author(s):  
Elisabeth C. Roberts ◽  
Paul S. Shapiro ◽  
Theresa Stines Nahreini ◽  
Gilles Pages ◽  
Jacques Pouyssegur ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Erk Pathway ◽  
Cycle Progression ◽  
Mitotic Entry ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Phosphoinositide 3 Kinase ◽  
And Function

ABSTRACT Mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K) pathways are necessary for cell cycle progression into S phase; however the importance of these pathways after the restriction point is poorly understood. In this study, we examined the regulation and function of extracellular signal-regulated kinase (ERK) and PI3K during G2/M in synchronized HeLa and NIH 3T3 cells. Phosphorylation and activation of both the MAP kinase kinase/ERK and PI3K/Akt pathways occur in late S and persist until the end of mitosis. Signaling was rapidly reversed by cell-permeable inhibitors, indicating that both pathways are continuously activated and rapidly cycle between active and inactive states during G2/M. The serum-dependent behavior of PI3K/Akt versus ERK pathway activation indicates that their mechanisms of regulation differ during G2/M. Effects of cell-permeable inhibitors and dominant-negative mutants show that both pathways are needed for mitotic progression. However, inhibiting the PI3K pathway interferes with cdc2 activation, cyclin B1 expression, and mitotic entry, whereas inhibiting the ERK pathway interferes with mitotic entry but has little effect on cdc2 activation and cyclin B1 and retards progression from metaphase to anaphase. Thus, our study provides novel evidence that ERK and PI3K pathways both promote cell cycle progression during G2/M but have different regulatory mechanisms and function at distinct times.

scholarly journals (S)-10-Hydroxycamptothecin Inhibits Esophageal Squamous Cell Carcinoma Growth In Vitro and In Vivo Via Decreasing Topoisomerase I Enzyme Activity

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1964 ◽  
Author(s):  
Mengqiu Song ◽  
Shuying Yin ◽  
Ran Zhao ◽  
Kangdong Liu ◽  
Joydeb Kumar Kundu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Enzymatic Activity ◽  
Topoisomerase I ◽  
Cell Cycle Progression ◽  
Caspase 3 ◽  
Cyclin B1 ◽  
Phase Cell ◽  
Cycle Progression

Topoisomerase (TOP) I plays a major role in the process of supercoiled DNA relaxation, thereby facilitating DNA replication and cell cycle progression. The expression and enzymatic activity of TOP I is positively correlated with tumor progression. Although the anticancer activity of (S)-10-Hydroxycamptothecin (HCPT), a TOP I specific inhibitor, has been reported in various cancers, the effect of HCPT on esophageal cancer is yet to be examined. In this study, we investigate the potential of HCPT to inhibit the growth of ESCC cells in vitro and verify its anti-tumor activity in vivo by using a patient-derived xenograft (PDX) tumor model in mice. Our study revealed the overexpression of TOP I in ESCC cells and treatment with HCPT inhibited TOP I enzymatic activity at 24 h and decreased expression at 48 h and 72 h. HCPT also induced DNA damage by increasing the expression of H2A.XS139. HCPT significantly decreased the proliferation and anchorage-independent growth of ESCC cells (KYSE410, KYSE510, KYSE30, and KYSE450). Mechanistically, HCPT inhibited the G2/M phase cell cycle transition, decreased the expression of cyclin B1, and elevated p21 expression. In addition, HCPT stimulated ESCC cells apoptosis, which was associated with elevated expression of cleaved PARP, cleaved caspase-3, cleaved caspase-7, Bax, Bim, and inhibition of Bcl-2 expression. HCPT dramatically suppressed PDX tumor growth and decreased the expression of Ki-67 and TOP I and increased the level of cleaved caspase-3 and H2A.XS139 expression. Taken together, our data suggested that HCPT inhibited ESCC growth, arrested cell cycle progression, and induced apoptosis both in vitro and in vivo via decreasing the expression and activity of TOP I enzyme.

Cdk1-Dependent Phosphorylation ofNPM Overrides G2/M Checkpoint and Increases Leukemic Blasts in Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1322-1322
Author(s):  
Wei Du ◽  
Yun Zhou ◽  
Suzette Pike ◽  
Qishen Pang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Xenograft Model ◽  
Phosphorylation Sites ◽  
M Cell ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Cycle Arrest ◽  
Regulation Of Cell Cycle

Abstract An elevated level of nucleophosmin (NPM) is often found in actively proliferative cells including human tumors. To identify the regulatory role for NPM phosphorylation in proliferation and cell cycle control, a series of mutants targeting the consensus cyclin-dependent kinase (CKD) phosphorylation sites was created to mimic or abrogate either single-site or multi-site phosphorylation. Cells expressing the phosphomimetic NPM mutants showed enhanced proliferation and G2/M cell-cycle transition; whereas nonphosphorylatable mutants induced G2/M cell-cycle arrest. Simultaneous inactivation of two CKD phosphorylation sites at Ser10 and Ser70 (S10A/S70A, NPM-AA) induced phosphorylation of Cdk1 at Tyr15 (Cdc2Tyr15) and increased cytoplasmic accumulation of Cdc25C. Strikingly, stress-induced Cdk1Tyr15 and Cdc25C sequestration were completely suppressed by expression of a double phosphomimetic NPM mutant (S10E/S70E, NPM-EE). Further analysis revealed that phosphorylation of NPM at both Ser10 and Ser70 sites were required for proper interaction between Cdk1 and Cdc25C in mitotic cells. Moreover, the NPM-EE mutant directly bound to Cdc25C and prevented phosphorylation of Cdc25C at Ser216 during mitosis. Finally, NPM-EE overrided stress-induced G2/M arrest, increased peripheral-blood blasts and splenomegaly in a NOD/SCID xenograft model, and promoted leukemia development in Fanconi mouse hematopoietic stem/progenitor cells. Thus, these findings reveal a novel function of NPM on regulation of cell-cycle progression, in which Cdk1-dependent phosphorylation of NPM controls cell-cycle progression at G2/M transition through modulation of Cdc25C activity.

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