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 Repressed synthesis of ribosomal proteins generates protein-specific cell cycle and morphological phenotypes

2013 ◽  
Vol 24 (23) ◽  
pp. 3620-3633 ◽  
Author(s):  
Mamata Thapa ◽  
Ananth Bommakanti ◽  
Md. Shamsuzzaman ◽  
Brian Gregory ◽  
Leigh Samsel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Physical Structure ◽  
Specific Cell ◽  
M Cell ◽  
Cycle Progression ◽  
M Phase

The biogenesis of ribosomes is coordinated with cell growth and proliferation. Distortion of the coordinated synthesis of ribosomal components affects not only ribosome formation, but also cell fate. However, the connection between ribosome biogenesis and cell fate is not well understood. To establish a model system for inquiries into these processes, we systematically analyzed cell cycle progression, cell morphology, and bud site selection after repression of 54 individual ribosomal protein (r-protein) genes in Saccharomyces cerevisiae. We found that repression of nine 60S r-protein genes results in arrest in the G2/M phase, whereas repression of nine other 60S and 22 40S r-protein genes causes arrest in the G1 phase. Furthermore, bud morphology changes after repression of some r-protein genes. For example, very elongated buds form after repression of seven 60S r-protein genes. These genes overlap with, but are not identical to, those causing the G2/M cell cycle phenotype. Finally, repression of most r-protein genes results in changed sites of bud formation. Strikingly, the r-proteins whose repression generates similar effects on cell cycle progression cluster in the ribosome physical structure, suggesting that different topological areas of the precursor and/or mature ribosome are mechanistically connected to separate aspects of the cell cycle.

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.

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.

scholarly journals Identification of Aurora-A as a Direct Target of E2F3 during G2/M Cell Cycle Progression

2008 ◽  
Vol 283 (45) ◽  
pp. 31012-31020 ◽  
Author(s):  
Lili He ◽  
Hua Yang ◽  
Yihong Ma ◽  
W. Jack Pledger ◽  
W. Douglas Cress ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Aurora A ◽  
M Cell ◽  
Cycle Progression ◽  
Direct Target

scholarly journals S100A8/A9 (Calprotectin) Negatively Regulates G2/M Cell Cycle Progression and Growth of Squamous Cell Carcinoma

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69395 ◽  
Author(s):  
Ali Khammanivong ◽  
Chengxing Wang ◽  
Brent S. Sorenson ◽  
Karen F. Ross ◽  
Mark C. Herzberg
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Cycle Progression ◽  
M Cell ◽  
Cycle Progression

scholarly journals Incompatibility between proliferation and plant invasion is mediated by a regulator of appressorium formation in the corn smut fungusUstilago maydis

2020 ◽  
Vol 117 (48) ◽  
pp. 30599-30609
Author(s):  
Antonio de la Torre ◽  
Sónia Castanheira ◽  
José Pérez-Martín
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Pathogenic Fungi ◽  
Phytopathogenic Fungi ◽  
Toggle Switch ◽  
Appressorium Formation ◽  
M Cell ◽  
Gene Encoding ◽  
Cycle Progression ◽  
Corn Smut

Plant pathogenic fungi often developed specialized infection structures to breach the outer surface of a host plant. These structures, called appressoria, lead the invasion of the plant by the fungal hyphae. Studies in different phytopathogenic fungi showed that appressorium formation seems to be subordinated to the cell cycle. This subordination ensures the loading in the invading hypha of the correct genetic information to proceed with plant infection. However, how the cell cycle transmits its condition to the genetic program controlling appressorium formation and promoting the plant’s invasion is unknown. Our results have uncovered how this process occurs for the appressorium ofUstilago maydis, the agent responsible for corn smut disease. Here, we described that the complex Clb2-cyclin-dependent kinase (Cdk)1, one of the master regulators of G2/M cell cycle progression inU. maydis, interacts and controls the subcellular localization of Biz1, a transcriptional factor required for the activation of the appressorium formation. Besides, Biz1 can arrest the cell cycle by down-regulation of the gene encoding a second b-cyclin Clb1 also required for the G2/M transition. These results revealed a negative feedback loop between appressorium formation and cell cycle progression inU. maydis, which serves as a “toggle switch” to control the fungal decision between infecting the plant or proliferating out of the plant.

scholarly journals Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System

2021 ◽  
Vol 8 ◽  
Author(s):  
Irene Delgado-Román ◽  
Mari Cruz Muñoz-Centeno
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Mrna Translation ◽  
Rna Polymerases ◽  
Specific Cell ◽  
Cycle Progression ◽  
Nuclear Rna

Eukaryotic life is possible due to the multitude of complex and precise phenomena that take place in the cell. Essential processes like gene transcription, mRNA translation, cell growth, and proliferation, or membrane traffic, among many others, are strictly regulated to ensure functional success. Such systems or vital processes do not work and adjusts independently of each other. It is required to ensure coordination among them which requires communication, or crosstalk, between their different elements through the establishment of complex regulatory networks. Distortion of this coordination affects, not only the specific processes involved, but also the whole cell fate. However, the connection between some systems and cell fate, is not yet very well understood and opens lots of interesting questions. In this review, we focus on the coordination between the function of the three nuclear RNA polymerases and cell cycle progression. Although we mainly focus on the model organism Saccharomyces cerevisiae, different aspects and similarities in higher eukaryotes are also addressed. We will first focus on how the different phases of the cell cycle affect the RNA polymerases activity and then how RNA polymerases status impacts on cell cycle. A good example of how RNA polymerases functions impact on cell cycle is the ribosome biogenesis process, which needs the coordinated and balanced production of mRNAs and rRNAs synthesized by the three eukaryotic RNA polymerases. Distortions of this balance generates ribosome biogenesis alterations that can impact cell cycle progression. We also pay attention to those cases where specific cell cycle defects generate in response to repressed synthesis of ribosomal proteins or RNA polymerases assembly defects.

scholarly journals Mdt1, a Novel Rad53 FHA1 Domain-Interacting Protein, Modulates DNA Damage Tolerance and G2/M Cell Cycle Progression in Saccharomycescerevisiae

2004 ◽  
Vol 24 (7) ◽  
pp. 2779-2788 ◽  
Author(s):  
Brietta L. Pike ◽  
Suganya Yongkiettrakul ◽  
Ming-Daw Tsai ◽  
Jörg Heierhorst
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Structural Integrity ◽  
Damage Tolerance ◽  
Rna Recognition Motif ◽  
M Cell ◽  
Dna Damage Tolerance ◽  
Cycle Progression ◽  
Dependent Cell

ABSTRACT The Rad53 kinase plays a central role in yeast DNA damage checkpoints. Rad53 contains two FHA phosphothreonine-binding domains that are required for Rad53 activation and possibly downstream signaling. Here we show that the N-terminal Rad53 FHA1 domain interacts with the RNA recognition motif, coiled-coil, and SQ/TQ cluster domain-containing protein Mdt1 (YBl051C). The interaction of Rad53 and Mdt1 depends on the structural integrity of the FHA1 phosphothreonine-binding site as well as threonine-305 of Mdt1. Mdt1 is constitutively threonine phosphorylated and hyperphosphorylated in response to DNA damage in vivo. DNA damage-dependent Mdt1 hyperphosphorylation depends on the Mec1 and Tel1 checkpoint kinases, and Mec1 can directly phosphorylate a recombinant Mdt1 SQ/TQ domain fragment. MDT1 overexpression is synthetically lethal with a rad53 deletion, whereas mdt1 deletion partially suppresses the DNA damage hypersensitivity of checkpoint-compromised strains and generally improves DNA damage tolerance. In the absence of DNA damage, mdt1 deletion leads to delayed anaphase completion, with an elongated cell morphology reminiscent of that of G2/M cell cycle mutants. mdt1-dependent and DNA damage-dependent cell cycle delays are not additive, suggesting that they act in the same pathway. The data indicate that Mdt1 is involved in normal G2/M cell cycle progression and is a novel target of checkpoint-dependent cell cycle arrest pathways.

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