scholarly journals A Forkhead Transcription Factor Is Important for True Hyphal as well as Yeast Morphogenesis in Candida albicans

2002 ◽  
Vol 1 (5) ◽  
pp. 787-798 ◽  
Author(s):  
Eric S. Bensen ◽  
Scott G. Filler ◽  
Judith Berman
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Cycle Progression ◽  
Forkhead Transcription Factors

ABSTRACT Candida albicans is an important pathogen of immunocompromised patients which grows with true hyphal, pseudohyphal, and yeast morphologies. The dynamics of cell cycle progression are markedly different in true hyphal relative to pseudohyphal and yeast cells, including nuclear movement and septin ring positioning. In Saccharomyces cerevisiae, two forkhead transcription factors (ScFKH1 and ScFKH2) regulate the expression of B-cyclin genes. In both S. cerevisiae and Schizosaccharomyces pombe, forkhead transcription factors also influence morphogenesis. To explore the molecular mechanisms that connect C. albicans morphogenesis with cell cycle progression, we analyzed CaFKH2, the single homolog of S. cerevisiae FKH1/FKH2. C. albicans cells lacking CaFkh2p formed constitutive pseudohyphae under all yeast and hyphal growth conditions tested. Under hyphal growth conditions levels of hyphae-specific mRNAs were reduced, and under yeast growth conditions levels of several genes encoding proteins likely to be important for cell wall separation were reduced. Together these results imply that Fkh2p is required for the morphogenesis of true hyphal as well as yeast cells. Efg1p and Cph1p, two transcription factors that contribute to C. albicans hyphal growth, were not required for the pseudohyphal morphology of fkh2 mutants, implying that Fkh2p acts in pathways downstream of and/or parallel to Efg1p and Cph1p. In addition, cells lacking Fkh2p were unable to damage human epithelial or endothelial cells in vitro, suggesting that Fkh2p contributes to C. albicans virulence.

A putative dual-specific protein phosphatase encoded by YVH1 controls growth, filamentation and virulence in Candida albicans

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2223-2232 ◽  
Author(s):  
Nozomu Hanaoka ◽  
Takashi Umeyama ◽  
Keigo Ueno ◽  
Kenji Ueda ◽  
Teruhiko Beppu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Cell Cycle Progression ◽  
Germ Tube ◽  
Hyphal Growth ◽  
Tube Formation ◽  
Yeast Cells ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Cycle Progression

In response to stimulants, such as serum, the yeast cells of the opportunistic fungal pathogen Candida albicans form germ tubes, which develop into hyphae. Yvh1p, one of the 29 protein phosphatases encoded in the C. albicans genome, has 45 % identity with the dual-specific phosphatase Yvh1p of the model yeast Saccharomyces cerevisiae. In this study, Yvh1p expression was not observed during the initial step of germ tube formation, although Yvh1p was expressed constitutively in cell cycle progression of yeast or hyphal cells. In an attempt to analyse the function of Yvh1p phosphatase, the complete ORFs of both alleles were deleted by replacement with hph200–URA3–hph200 and ARG4. Although YVH1 has nine single-nucleotide polymorphisms in its coding sequence, both YVH1 alleles were able to complement the YVH1 gene disruptant. The vegetative growth of Δyvh1 was significantly slower than the wild-type. The hyphal growth of Δyvh1 on agar, or in a liquid medium, was also slower than the wild-type because of the delay in nuclear division and septum formation, although germ tube formation was similar between the wild-type and the disruptant. Despite the slow hyphal growth, the expression of several hypha-specific genes in Δyvh1 was not delayed or repressed compared with that of the wild-type. Infection studies using mouse models revealed that the virulence of Δyvh1 was less than that of the wild-type. Thus, YVH1 contributes to normal vegetative yeast or hyphal cell cycle progression and pathogenicity, but not to germ tube formation.

scholarly journals Multiple inputs ensure yeast cell size homeostasis during cell cycle progression

2017 ◽  
Author(s):  
Cecilia Garmendia-Torres ◽  
Olivier Tassy ◽  
Audrey Matifas ◽  
Nacho Molina ◽  
Gilles Charvin
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Size Control ◽  
Large Cell ◽  
Yeast Cells ◽  
Cycle Progression ◽  
Size Variability

AbstractCoordination of cell growth and division is essential for proper cell function. In budding yeast, although some molecular mechanisms responsible for cell size control during G1 have been elucidated, the mechanism by which cell size homeostasis is established and maintained throughout the cell cycle remains to be discovered. Here, we developed a new technique based on quantification of histone levels to monitor cell cycle progression in individual yeast cells with unprecedented accuracy. Our analysis establishes the existence of a strong mechanism controlling bud size in G2/M that prevents premature entry into mitosis, and contributes significantly to the overall control of size variability during the cell cycle. While most G1/S regulation mutants do not display any strongly impaired size homeostasis, mutants in which B-type cyclin regulation is altered display large cell-to-cell size variability. Our study thus demonstrates that size homeostasis is not controlled by a G1-specific mechanism but is likely to be an emergent property resulting from the integration of several mechanisms, including the control of cyclin B-Cdk activity, that coordinate cell and bud growth with division.

scholarly journals A G1 Cyclin Is Necessary for Maintenance of Filamentous Growth in Candida albicans

1999 ◽  
Vol 19 (6) ◽  
pp. 4019-4027 ◽  
Author(s):  
Jonathan D. J. Loeb ◽  
Marisa Sepulveda-Becerra ◽  
Idit Hazan ◽  
Haoping Liu
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Cell Cycle Progression ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Specific Expression ◽  
Molecular Control ◽  
Solid Media ◽  
Specific Expression Pattern ◽  
Germ Tubes

ABSTRACT Candida albicans undergoes a dramatic morphological transition in response to various growth conditions. This ability to switch from a yeast form to a hyphal form is required for its pathogenicity. The intractability of Candida to traditional genetic approaches has hampered the study of the molecular mechanism governing this developmental switch. Our approach is to use the more genetically tractable yeast Saccharomyces cerevisiae to yield clues about the molecular control of filamentation for further studies in Candida. G1 cyclins Cln1 and Cln2 have been implicated in the control of morphogenesis in S. cerevisiae. We show that C. albicans CLN1(CaCLN1) has the same cell cycle-specific expression pattern as CLN1 and CLN2 of S. cerevisiae. To investigate whether G1 cyclins are similarly involved in the regulation of cell morphogenesis during the yeast-to-hypha transition of C. albicans, we mutatedCaCLN1. Cacln1/Cacln1 cells were found to be slower than wild-type cells in cell cycle progression. TheCacln1/Cacln1 mutants were also defective in hyphal colony formation on several solid media. Furthermore, while mutant strains developed germ tubes under several hypha-inducing conditions, they were unable to maintain the hyphal growth mode in a synthetic hypha-inducing liquid medium and were deficient in the expression of hypha-specific genes in this medium. Our results suggest that CaCln1 may coordinately regulate hyphal development with signal transduction pathways in response to various environmental cues.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length

2017 ◽  
Author(s):  
Shixuan Liu ◽  
Miriam B. Ginzberg ◽  
Nish Patel ◽  
Marc Hild ◽  
Bosco Leung ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
P38 Mapk ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Small Cells ◽  
Animal Cells ◽  
Cycle Progression ◽  
Size Uniformity

AbstractAnimal cells within a tissue typically display a striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown that size uniformity in animal cells is promoted, in part, by size-dependent regulation of G1 length. To identify the molecular mechanisms underlying this process, we performed a large-scale small molecule screen and found that the p38 MAPK pathway is involved in coordinating cell size and cell cycle progression. Small cells display higher p38 activity and spend more time in G1 than larger cells. Inhibition of p38 MAPK leads to loss of the compensatory G1 length extension in small cells, resulting in faster proliferation, smaller cell size and increased size heterogeneity. We propose a model wherein the p38 pathway responds to changes in cell size and regulates G1 exit accordingly, to increase cell size uniformity.One-sentence summaryThe p38 MAP kinase pathway coordinates cell growth and cell cycle progression by lengthening G1 in small cells, allowing them more time to grow before their next division.

Abstract W P198: Sphingomyelin Synthases Regulate Neuronal Cell Proliferation and Cell Cycle Progression

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Umadevi V Wesley ◽  
Daniel Tremmel ◽  
Robert Dempsey
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Artery Occlusion ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Cycle Regulation ◽  
Cerebral Artery Occlusion

Introduction: The molecular mechanisms of cerebral ischemia damage and protection are not completely understood, but a number of reports implicate the contribution of lipid metabolism and cell-cycle regulating proteins in stroke out come. We have previously shown that tricyclodecan-9-yl-xanthogenate (D609) resulted in increased ceramide levels after transient middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR). We hypothesized that D609 induced cell cycle arrest probably by inhibiting sphingomyelin synthase (SMS). In this study, we examined the direct effects of SMS on cell cycle progression and proliferation of neuroblast cells. Methods: Ischemia was induced by middle cerebral artery occlusion (MCAO) and reperfusion. Expression levels were measured by western blot analysis, RT-PCR, and Immunofluorescence staining. SMS1 and 2 expressions were silenced by stable transfection with SMS1/2-targeted shRNA. Cell cycle analysis was performed using Flow cytometry. Data were analyzed using MODFIT cell cycle analysis program. Cell proliferation rate was measured by MTT assay. Results: We have identified that the expression of SMS1is significantly up-regulated in the ischemic hemisphere following MCAO. Neuro-2a cells transfected with SMS specific ShRNA acquired more neuronal like phenotype and exhibited decreased proliferation rate. Also, silencing of both SMS1 and 2 induced cell-cycle arrest as shown by significantly increased percentage of cells in G0/G1 and decreased proportion of cells in S-phase as compared to control cells. This was accompanied by up-regulation of cyclin-dependent kinase (Cdk) inhibitors p21 and decreased levels of phophorylated AKT levels. Furthermore, loss of SMS inhibited the migratory potential of Neuro 2a cells. Summary: Up-regulation of SMS under ischemic/reperfusion conditions suggests that this enzyme potentially contributes to cell cycle regulation and may contribute to maintaining neuronal cell population. Further studies may open up a new direction for identifying the molecular mechanisms of cell cycle regulation and protection following ischemic stroke

scholarly journals Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1384 ◽  
Author(s):  
Shang-Tse Ho ◽  
Chi-Chen Lin ◽  
Yu-Tang Tung ◽  
Jyh-Horng Wu
Keyword(s):  
Cell Cycle ◽  
Antitumor Activity ◽  
Lung Adenocarcinoma ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Microtubule Dynamics ◽  
Cycle Progression ◽  
Human Lung Adenocarcinoma

Yatein is an antitumor agent isolated from Calocedrus formosana Florin leaves extract. In our previous study, we found that yatein inhibited the growth of human lung adenocarcinoma A549 and CL1-5 cells by inducing intrinsic and extrinsic apoptotic pathways. To further uncover the effects and mechanisms of yatein-induced inhibition on A549 and CL1-5 cell growth, we evaluated yatein-mediated antitumor activity in vivo and the regulatory effects of yatein on cell-cycle progression and microtubule dynamics. Flow cytometry and western blotting revealed that yatein induces G2/M arrest in A549 and CL1-5 cells. Yatein also destabilized microtubules and interfered with microtubule dynamics in the two cell lines. Furthermore, we evaluated the antitumor activity of yatein in vivo using a xenograft mouse model and found that yatein treatment altered cyclin B/Cdc2 complex expression and significantly inhibited tumor growth. Taken together, our results suggested that yatein effectively inhibited the growth of A549 and CL1-5 cells possibly by disrupting cell-cycle progression and microtubule dynamics.

scholarly journals Compartmentalized nodes control mitotic entry signaling in fission yeast

2013 ◽  
Vol 24 (12) ◽  
pp. 1872-1881 ◽  
Author(s):  
Lin Deng ◽  
James B. Moseley
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Fission Yeast ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Interaction Network ◽  
Yeast Cells ◽  
Cell Cortex ◽  
Cycle Progression ◽  
Mitotic Entry

Cell cycle progression is coupled to cell growth, but the mechanisms that generate growth-dependent cell cycle progression remain unclear. Fission yeast cells enter into mitosis at a defined size due to the conserved cell cycle kinases Cdr1 and Cdr2, which localize to a set of cortical nodes in the cell middle. Cdr2 is regulated by the cell polarity kinase Pom1, suggesting that interactions between cell polarity proteins and the Cdr1-Cdr2 module might underlie the coordination of cell growth and division. To identify the molecular connections between Cdr1/2 and cell polarity, we performed a comprehensive pairwise yeast two-hybrid screen. From the resulting interaction network, we found that the protein Skb1 interacted with both Cdr1 and the Cdr1 inhibitory target Wee1. Skb1 inhibited mitotic entry through negative regulation of Cdr1 and localized to both the cytoplasm and a novel set of cortical nodes. Skb1 nodes were distinct structures from Cdr1/2 nodes, and artificial targeting of Skb1 to Cdr1/2 nodes delayed entry into mitosis. We propose that the formation of distinct node structures in the cell cortex controls signaling pathways to link cell growth and division.

scholarly journals B Lymphocytes Differentially Use the Rel and Nuclear Factor κB1 (NF-κB1) Transcription Factors to Regulate Cell Cycle Progression and Apoptosis in Quiescent and Mitogen-activated Cells

1998 ◽  
Vol 187 (5) ◽  
pp. 663-674 ◽  
Author(s):  
Raelene J. Grumont ◽  
Ian J. Rourke ◽  
Lorraine A. O'Reilly ◽  
Andreas Strasser ◽  
Kensuke Miyake ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Transcription Factors ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Cycle Progression ◽  
Nuclear Factor ◽  
Cycle Progression ◽  
Regulate Cell Cycle Progression

Rel and nuclear factor (NF)-κB1, two members of the Rel/NF-κB transcription factor family, are essential for mitogen-induced B cell proliferation. Using mice with inactivated Rel or NF-κB1 genes, we show that these transcription factors differentially regulate cell cycle progression and apoptosis in B lymphocytes. Consistent with an increased rate of mature B cell turnover in naive nfkb1−/− mice, the level of apoptosis in cultures of quiescent nfkb1−/−, but not c-rel−/−, B cells is higher. The failure of c-rel−/− or nfkb1−/− B cells to proliferate in response to particular mitogens coincides with a cell cycle block early in G1 and elevated cell death. Expression of a bcl-2 transgene prevents apoptosis in resting and activated c-rel−/− and nfkb1−/− B cells, but does not overcome the block in cell cycle progression, suggesting that the impaired proliferation is not simply a consequence of apoptosis and that Rel/NF-κB proteins regulate cell survival and cell cycle control through independent mechanisms. In contrast to certain B lymphoma cell lines in which mitogen-induced cell death can result from Rel/NF-κB–dependent downregulation of c-myc, expression of c-myc is normal in resting and stimulated c-rel−/− B cells, indicating that target gene(s) regulated by Rel that are important for preventing apoptosis may differ in normal and immortalized B cells. Collectively, these results are the first to demonstrate that in normal B cells, NF-κB1 regulates survival of cells in G0, whereas mitogenic activation induced by distinct stimuli requires different Rel/NF-κB factors to control cell cycle progression and prevent apoptosis.

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