scholarly journals Induction of S. cerevisiae Filamentous Differentiation by Slowed DNA Synthesis Involves Mec1, Rad53 and Swe1 Checkpoint Proteins

2003 ◽  
Vol 14 (12) ◽  
pp. 5116-5124 ◽  
Author(s):  
Yi Wei Jiang ◽  
Christopher Minkyu Kang
Keyword(s):  
Dna Synthesis ◽  
Nitrogen Starvation ◽  
Model Organism ◽  
Filamentous Growth ◽  
Mitogen Activated Protein Kinase ◽  
Cell Cycle Regulators ◽  
Checkpoint Proteins ◽  
The Core ◽  
Mitogen Activated Protein ◽  
Mitotic Cyclin

A key question in eukaryotic differentiation is whether there are common regulators or biochemical events that are required for diverse types of differentiation or whether there is a core mechanism for differentiation. The unicellular model organism Saccharomyces cerevisiae undergoes filamentous differentiation in response to environmental cues. Because conserved cell cycle regulators, the mitotic cyclin-dependent kinase Clb2/Cdc28, and its inhibitor Swe1 were found to be involved in both nitrogen starvation- and short chain alcohol-induced filamentous differentiation, they were identified as components of the core mechanism for filamentous differentiation. We report here that slowed DNA synthesis also induces yeast filamentous differentiation through conserved checkpoint proteins Mec1 and Rad53. Swe1 and Clb2 are also involved in this form of differentiation, and the core status of Swe1/Clb2/Cdc28 in the mechanism of filamentous differentiation has therefore been confirmed. Because the cAMP and filamentous growth mitogen-activated protein kinase pathways that mediate nitrogen starvation-induced filamentous differentiation are not required for slowed DNA synthesis-induced filamentous growth, they can therefore be excluded from the core mechanism. More significantly, slowed DNA synthesis also induces differentiation in mammalian cancer cells, and such stimulus conservation may indicate that the core mechanism for yeast filamentous differentiation is conserved in mammalian differentiation.

scholarly journals The Ustilago maydis ubc4 and ubc5 Genes Encode Members of a MAP Kinase Cascade Required for Filamentous Growth

2000 ◽  
Vol 13 (7) ◽  
pp. 781-786 ◽  
Author(s):  
David L. Andrews ◽  
John D. Egan ◽  
María E. Mayorga ◽  
Scott E. Gold
Keyword(s):  
Map Kinase ◽  
Ustilago Maydis ◽  
Filamentous Growth ◽  
Mitogen Activated Protein Kinase ◽  
Genetic Determinants ◽  
Map Kinase Cascade ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Suppressor Mutants ◽  
Corn Smut

Ustilago maydis, the causal agent of corn smut disease, displays dimorphic growth in which it alternates between a budding haploid saprophyte and a filamentous dikaryotic pathogen. We are interested in identifying the genetic determinants of filamentous growth and pathogenicity in U. maydis. To do this we have taken a forward genetic approach. Earlier, we showed that haploid adenylate cyclase (uac1) mutants display a constitutively filamentous phenotype. Mutagenesis of a uac1 disruption strain allowed the isolation of a large number of budding suppressor mutants. These mutants are named ubc, for Ustilago bypass of cyclase, as they no longer require the production of cyclic AMP (cAMP) to grow in the budding morphology. Complementation of a subset of these suppressor mutants led to the identification of the ubc4 and ubc5 genes, which are required for filamentous growth and encode a MAP (mitogen-activated protein) kinase kinase kinase and a MAP kinase kinase, respectively. Evidence suggests that they are important in the pheromone response pathway and in pathogenicity. These results further support an important interplay of the cAMP and MAP kinase signal transduction pathways in the control of morphogenesis and pathogenicity in U. maydis.

scholarly journals Stimulation of DNA synthesis by natural ceramide 1-phosphate

1997 ◽  
Vol 325 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Antonio GOMEZ-MUÑOZ ◽  
Laura M. FRAGO ◽  
Luis ALVAREZ ◽  
Isabel VARELA-NIETO
Keyword(s):  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Solvent Mixture ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Antigen ◽  
Tyrosine Residues ◽  
Mitogen Activated Protein ◽  
Ceramide 1 ◽  
Proliferating Cell ◽  
Stimulation Of

We found that natural (long-chain) ceramide 1-phosphate can be dispersed into aqueous solution when dissolved in an appropriate mixture of methanol/dodecane (49:1, v/v). This solvent mixture facilitates the interaction of this phosphosphingolipid with cells. Under these conditions, incubation of EGFR T17 fibroblasts with natural ceramide 1-phosphate caused a potent stimulation of DNA synthesis. This effect was accompanied by an increase in the levels of proliferating-cell nuclear antigen. Concentrations of natural ceramide 1-phosphate that stimulated the synthesis of DNA did not inhibit adenylate cyclase activity, nor did they stimulate phospholipase D. Natural ceramide 1-phosphate did not alter the cellular phosphorylation state of tyrosine residues or of mitogen-activated protein kinase. Furthermore, natural ceramide 1-phosphate failed to induce the expression of the proto-oncogenes c-myc and c-fos. Both the stimulation of DNA synthesis and the induction of proliferating-cell nuclear antigen by natural ceramide 1-phosphate were inhibited by natural ceramides. This work suggests that the use of methanol and dodecane to deliver natural ceramide 1-phosphate to cells may be useful for elucidation of the biological function(s) and mechanism(s) of action of ceramide 1-phosphate.

scholarly journals The Basic Leucine Zipper Domain Transcription Factor Atf1 Directly Controls Cdc13 Expression and Regulates Mitotic Entry Independently of Wee1 and Cdc25 in Schizosaccharomyces pombe

2014 ◽  
Vol 13 (6) ◽  
pp. 813-821 ◽  
Author(s):  
Sushobhana Bandyopadhyay ◽  
Isha Dey ◽  
Megalakshmi Suresh ◽  
Geetanjali Sundaram
Keyword(s):  
Transcription Factor ◽  
Schizosaccharomyces Pombe ◽  
Leucine Zipper ◽  
Mitogen Activated Protein Kinase ◽  
Cyclin Dependent Kinase ◽  
Basic Leucine Zipper ◽  
Content Type ◽  
Mitogen Activated Protein ◽  
Mitotic Cyclin ◽  
Approaches To Study

ABSTRACTProgression into mitosis is a major point of regulation in theSchizosaccharomyces pombecell cycle, and its proper control is essential for maintenance of genomic stability. Investigation of the G2/M progression event inS. pombehas revealed the existence of a complex regulatory process that is responsible for making the decision to enter mitosis. Newer aspects of this regulation are still being revealed. In this paper, we report the discovery of a novel mode of regulation of G2/M progression inS. pombe. We show that the mitogen-activated protein kinase (MAPK)-regulated transcription factor Atf1 is a regulator of Cdc13 (mitotic cyclin) transcription and is therefore a prominent player in the regulation of mitosis inS. pombe. We have used genetic approaches to study the effect of overexpression or deletion of Atf1 on the cell length and G2/M progression ofS. pombecells. Our results clearly show that Atf1 overexpression accelerates mitosis, leading to an accumulation of cells with shorter lengths. The previously known major regulators of entry into mitosis are the Cdc25 phosphatase and the Wee1 kinase, which modulate cyclin-dependent kinase (CDK) activity. The significantly striking aspect of our discovery is that Atf1-mediated G2/M progression is independent of both Cdc25 and Wee1. We have shown that Atf1 binds to the Cdc13 promoter, leading to activation of Cdc13 expression. This leads to enhanced nuclear localization of CDK Cdc2, thereby promoting the G2/M transition.

scholarly journals Cdc42p-Interacting Protein Bem4p Regulates the Filamentous-Growth Mitogen-Activated Protein Kinase Pathway

2014 ◽  
Vol 35 (2) ◽  
pp. 417-436 ◽  
Author(s):  
Andrew Pitoniak ◽  
Colin A. Chavel ◽  
Jacky Chow ◽  
Jeremy Smith ◽  
Diawoye Camara ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mapk Pathway ◽  
Filamentous Growth ◽  
Cell Polarization ◽  
Mitogen Activated Protein Kinase ◽  
Specific Response ◽  
Ph Domain ◽  
Interacting Protein ◽  
Mitogen Activated Protein ◽  
Growth Pathway

The ubiquitous Rho (Ras homology) GTPase Cdc42p can function in different settings to regulate cell polarity and cellular signaling. How Cdc42p and other proteins are directed to function in a particular context remains unclear. We show that the Cdc42p-interacting protein Bem4p regulates the mitogen-activated protein kinase (MAPK) pathway that controls filamentous growth inSaccharomyces cerevisiae. Bem4p controlled the filamentous-growth pathway but not other MAPK pathways (mating or high-osmolarity glycerol response [HOG]) that also require Cdc42p and other shared components. Bem4p associated with the plasma membrane (PM) protein, Sho1p, to regulate MAPK activity and cell polarization under nutrient-limiting conditions that favor filamentous growth. Bem4p also interacted with the major activator of Cdc42p, the guanine nucleotide exchange factor (GEF) Cdc24p, which we show also regulates the filamentous-growth pathway. Bem4p interacted with the pleckstrin homology (PH) domain of Cdc24p, which functions in an autoinhibitory capacity, and was required, along with other pathway regulators, to maintain Cdc24p at polarized sites during filamentous growth. Bem4p also interacted with the MAPK kinase kinase (MAPKKK) Ste11p. Thus, Bem4p is a new regulator of the filamentous-growth MAPK pathway and binds to general proteins, like Cdc42p and Ste11p, to promote a pathway-specific response.

scholarly journals Comparative Analysis of Transmembrane Regulators of the Filamentous Growth Mitogen-Activated Protein Kinase Pathway Uncovers Functional and Regulatory Differences

2015 ◽  
Vol 14 (9) ◽  
pp. 868-883 ◽  
Author(s):  
Hema Adhikari ◽  
Lauren M. Caccamise ◽  
Tanaya Pande ◽  
Paul J. Cullen
Keyword(s):  
Protein Kinase ◽  
Mapk Pathway ◽  
Filamentous Growth ◽  
Mapk Signaling ◽  
Fine Tuning ◽  
Mitogen Activated Protein Kinase ◽  
Rate Limiting Step ◽  
Mitogen Activated Protein ◽  
Multiple Signaling ◽  
Growth Pathway

ABSTRACTFilamentous growth is a microbial differentiation response that involves the concerted action of multiple signaling pathways. In budding yeast, one pathway that regulates filamentous growth is a Cdc42p-dependent mitogen-activated protein kinase (MAPK) pathway. Several transmembrane (TM) proteins regulate the filamentous growth pathway, including the signaling mucin Msb2p, the tetraspan osmosensor Sho1p, and an adaptor Opy2p. The TM proteins were compared to identify common and unique features. Msb2p, Sho1p, and Opy2p associated by coimmunoprecipitation analysis but showed predominantly different localization patterns. The different localization patterns of the proteins resulted in part from different rates of turnover from the plasma membrane (PM). In particular, Msb2p (and Opy2p) were turned over rapidly compared to Sho1p. Msb2p signaled from the PM, and its turnover was a rate-limiting step in MAPK signaling. Genetic analysis identified unique phenotypes of cells overexpressing the TM proteins. Therefore, each TM regulator of the filamentous growth pathway has its own regulatory pattern and specific function in regulating filamentous growth. This specialization may be important for fine-tuning and potentially diversifying the filamentation response.

scholarly journals Menin Is a Regulator of the Stress Response in Drosophila melanogaster

2005 ◽  
Vol 25 (22) ◽  
pp. 9960-9972 ◽  
Author(s):  
Maria Papaconstantinou ◽  
Ying Wu ◽  
Hendrik Nikolaas Pretorius ◽  
Nishi Singh ◽  
Gabriella Gianfelice ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Rna Interference ◽  
Stress Response ◽  
Heat Shock ◽  
Model Organism ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Control Of Gene Expression ◽  
Damage Sensing ◽  
Mitogen Activated Protein

ABSTRACT Menin, the product of the multiple endocrine neoplasia type I gene, has been implicated in several biological processes, including the control of gene expression and apoptosis, the modulation of mitogen-activated protein kinase pathways, and DNA damage sensing or repair. In this study, we have investigated the function of menin in the model organism Drosophila melanogaster. We show that Drosophila lines overexpressing menin or an RNA interference for this gene develop normally but are impaired in their response to several stresses, including heat shock, hypoxia, hyperosmolarity and oxidative stress. In the embryo subjected to heat shock, this impairment was characterized by a high degree of developmental arrest and lethality. The overexpression of menin enhanced the expression of HSP70 in embryos and interfered with its down-regulation during recovery at the normal temperature. In contrast, the inhibition of menin with RNA interference reduced the induction of HSP70 and blocked the activation of HSP23 upon heat shock, Menin was recruited to the Hsp70 promoter upon heat shock and menin overexpression stimulated the activity of this promoter in embryos. A 70-kDa inducible form of menin was expressed in response to heat shock, indicating that menin is also regulated in conditions of stress. The induction of HSP70 and HSP23 was markedly reduced or absent in mutant embryos harboring a deletion of the menin gene. These embryos, which did not express the heat shock-inducible form of menin, were also hypersensitive to various conditions of stress. These results suggest a novel role for menin in the control of the stress response and in processes associated with the maintenance of protein integrity.

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