scholarly journals Deregulation of DSE1 Gene Expression Results in Aberrant Budding within the Birth Scar and Cell Wall Integrity Pathway Activation in Saccharomyces cerevisiae

2009 ◽  
Vol 8 (4) ◽  
pp. 586-594 ◽  
Author(s):  
Ivana Frýdlová ◽  
Ivana Malcová ◽  
Pavla Vašicová ◽  
Jiří Hašek
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Daughter Cell ◽  
Fluorescent Protein ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Protein ◽  
Cell Wall Integrity ◽  
Pathway Activation

ABSTRACT Strains of Saccharomyces cerevisiae lacking Isw2, the catalytic subunit of the Isw2 chromatin remodeling complex, show the mating type-independent activation of the cell wall integrity (CWI) signaling pathway. Since the CWI pathway activation usually reflects cell wall defects, we searched for the cell wall-related genes changed in expression. The genes DSE1, CTS1, and CHS1 were upregulated as a result of the absence of Isw2, according to previously published gene expression profiles (I. Frydlova, M. Basler, P. Vasicova, I. Malcova, and J. Hasek, Curr. Genet. 52:87-95, 2007). Western blot analyses of double deletion mutants, however, did not indicate the contribution of the chitin metabolism-related genes CTS1 and CHS1 to the CWI pathway activation. Nevertheless, the deletion of the DSE1 gene encoding a daughter cell-specific protein with unknown function suppressed CWI pathway activation in isw2Δ cells. In addition, the deletion of DSE1 also abolished the budding-within-the-birth-scar phenotype of isw2Δ cells. The plasmid-driven overexpression proved that the deregulation of Dse1 synthesis was also responsible for CWI pathway activation and manifestation of the budding-within-the-birth-scar phenotype in wild-type cells. The overproduced Dse1-green fluorescent protein localized to both sides of the septum and persisted in unbudded cells. Although the exact cellular role of this daughter cell-specific protein has to be elucidated, our data point to the involvement of Dse1 in bud site selection in haploid cells.

Gene Expression Profiles for Prognosis in MGUS, Coupled with Signatures of Oncogenic Pathway Deregulation Provide a Novel Approach for Selection of Molecular Targets in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 655-655
Author(s):  
Ariel Anguiano ◽  
Chaitanya Acharya ◽  
Kelly Salter ◽  
Daniel McCluskey ◽  
Christina Gasperetto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Signaling Pathways ◽  
Chromosomal Instability ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Oncogenic Pathways ◽  
Novel Approach ◽  
Pathway Activation ◽  
Plasma Cell Dyscrasias

Abstract Gene expression profiles that reflect unique aspects of biologic phenotypes and characterize the heterogeneity of monoclonal gammopathies may facilitate the development of a ‘signature’ that predicts the evolution of MGUS to multiple myeloma (MM). Furthermore, while most patients with MM are initially sensitive to therapy, resistance invariably develops. Thus, a need exits for novel therapeutic strategies targeting resistance-associated deregulated molecular pathways. Using previously-described methodologies that employ DNA microarray data in a cohort of 877 annotated samples from patients with plasma cell dyscrasias (MGUS, untreated MM and refractory MM), a complex multi-gene expression profile (‘metagene’) of 120 genes was identified that predicts risk of progression, from MGUS to MM. This analysis used an initial ‘test’ cohort of patients with MGUS that represented patients followed for a median of 36.4 months. At follow up, 11% of these patients were identified as having disease progression. Leave-one-out cross validation analysis within the test cohort revealed 95% accuracy. The ‘metagene model’ was also evaluated in a large independent validation cohort. Overexpressed genes in the predictive model represented those involved in the proteasome, RAS, and MAP-kinase pathways. In addition, we used gene expression signatures that reflect the deregulation of major oncogenic signaling pathways (Ras, PI3kinase, Akt, Src, ß-catenin, E2F, and Myc) and pathways representative of the tumor microenvironment (Hypoxia, Angiogenesis, Chromosomal Instability, and TNF-alpha) to identify patterns of pathway activation unique to individual patients with plasma cell dyscrasias. This analysis revealed that patterns of pathway activation clearly defined the stages of myeloma progression. As an example, Myc deregulation was unique to refractory MM (p < 0.001) as compared to Ras and PI3K activation in MGUS patients (p < 0.01). Also, unique to refractory MM, a majority of the tumors (> 96%) had deregulation of multiple signaling pathways, suggesting a complex oncogenic process. In particular, these samples demonstrated deregulation in Ras (78%), Myc (70%), Src (63%), E2F (52%) and ß-catenin (52%) pathways. In contrast, normal plasma cells showed none to minimal deregulation of the oncogenic pathways. As a proof of concept, we then used cell proliferation assays to show that the predicted deregulation of Ras, Src and PI3 kinase pathways was directly proportional (p < 0.01, log rank test) to the sensitivity of cell lines (n = 17) to agents (FTS, SU6656, and LY4002 respectively) that specifically target these pathways. This suggests that in addition to identifying a high-risk cohort of patients with MGUS, such a strategy provides a novel approach to targeted therapeutics in refractory MM - by guiding the appropriate use of pathway specific inhibitors. Finally, results of Kaplan Meier analyses using gene expression-based classifiers and risk stratification models as well as further in vitro data involving manipulation of other oncogenic pathways and signatures relevant to myeloma (e.g. hypoxia, chromosomal instability and angiogenesis) will be also be presented.

Activation of intracellular signaling pathways as a new type of biomarkers for selection of target anticancer drugs.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23142-e23142 ◽  
Author(s):  
Anton Buzdin ◽  
Maxim Sorokin ◽  
Alexander Glusker ◽  
Andrew Garazha ◽  
Elena Poddubskaya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Patients ◽  
Intracellular Signaling ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Targets ◽  
Signalling Pathways ◽  
Pathway Activation ◽  
Significant Difference ◽  
Selection Of

e23142 Background: Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in tumorigenesis. More than 150 different ATDs have been approved for clinical use worldwide, and the clinicians are faced with the problem of choosing the best therapeutic solution for each patient. The problem of efficient ATD selection remains largely unsolved and personalized approaches are needed to select the best ATD candidates for individual patients. Methods: We propose a new approach termed OncoFinder. It is based on digesting gene expression profiles for the analysis of activation of intracellular signalling pathways as a marker for the selection of target therapies. The original bioinformatic algorithms were integrated with the databases featuring molecular drug targets, compositions of signalling pathways, including the functional role of each gene product, for more than 1700 pathways (Buzdin, Front.Genet 2014; Ozerov, Nature Communications 2016). Results: We showed that pathway activation strengths are more stable and reliable biomarkers of cancer than the expressions of individual genes. OncoFinder allows to detect changes at the level of pathway activation and to predict the effectiveness of drugs based on the knowledge of their molecular targets. We applied it to find new biomarkers of clinical response to the ATD cetuximab; for modelling the combined chemotherapy of acute myeloid leukemia and combined anti-VEGF/BRAF therapy of melanoma. For two unrelated datasets obtained for colon cancer patients before treatment with the ATD bevacizumab, we were able to distinguish between those who responded to treatment and not (p < 0.01). We next assayed biopsies for kidney cancer patients with known responses to the ATD sorafenib. The responders and non-responders showed a significant difference (p = 0.02). Finally, the OncoFinder platform was prospectively used for decision making support to patients with advanced metastatic solid tumors (n = 23). The efficiency of the ATD treatment was 61% (complete + partial response, RECIST). Conclusions: OncoFinder method may be effective for predicting response to ATD based on high throughput gene expression profiles.

scholarly journals Gene Expression ofPneumocystis murinaafter Treatment with Anidulafungin Results in Strong Signals for Sexual Reproduction, Cell Wall Integrity, and Cell Cycle Arrest, Indicating a Requirement for Ascus Formation for Proliferation

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Melanie T. Cushion ◽  
Alan Ashbaugh ◽  
Keeley Hendrix ◽  
Michael J. Linke ◽  
Nikeya Tisdale ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Wall ◽  
Life Cycle ◽  
Cell Cycle Arrest ◽  
Expression Profiles ◽  
Life Cycle Stage ◽  
Cell Wall Integrity ◽  
Content Type ◽  
Cycle Arrest

ABSTRACTThe echinocandins are a class of antifungal agents that target β-1,3-d-glucan (BG) biosynthesis. In the ascigerousPneumocystisspecies, treatment with these drugs depletes the ascus life cycle stage, which contains BG, but large numbers of forms which do not express BG remain in the infected lungs. In the present study, the gene expression profiles ofPneumocystis murinawere compared between infected, untreated mice and mice treated with anidulafungin for 2 weeks to understand the metabolism of the persisting forms. Almost 80 genes were significantly up- or downregulated. Like other fungi exposed to echinocandins, genes associated with sexual replication, cell wall integrity, cell cycle arrest, and stress comprised the strongest upregulated signals inP. murinafrom the treated mice. The upregulation of theP. murinaβ-1,3-d-glucan endohydrolase and endo-1,3-glucanase was notable and may explain the disappearance of the existing asci in the lungs of treated mice since both enzymes can degrade BG. The biochemical measurement of BG in the lungs of treated mice and fluorescence microscopy with an anti-BG antibody supported the loss of BG. Downregulated signals included genes involved in cell replication, genome stability, and ribosomal biogenesis and function and thePneumocystis-specific genes encoding the major surface glycoproteins (Msg). These studies suggest thatP. murinaattempted to undergo sexual replication in response to a stressed environment and was halted in any type of proliferative cycle, likely due to a lack of BG. Asci appear to be a required part of the life cycle stage ofPneumocystis, and BG may be needed to facilitate progression through the life cycle via sexual replication.

scholarly journals Short De-Etiolation Increases the Rooting of VC801 Avocado Rootstock

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1481
Author(s):  
Zvi Duman ◽  
Gal Hadas-Brandwein ◽  
Avi Eliyahu ◽  
Eduard Belausov ◽  
Mohamad Abu-Abied ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Wall ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pectin Methylesterase ◽  
Adventitious Root Formation ◽  
Fine Tuning ◽  
Wall Properties ◽  
Cell Wall Properties ◽  
Better Than

Dark-grown (etiolated) branches of many recalcitrant plant species root better than their green counterparts. Here it was hypothesized that changes in cell-wall properties and hormones occurring during etiolation contribute to rooting efficiency. Measurements of chlorophyll, carbohydrate and auxin contents, as well as tissue compression, histological analysis and gene-expression profiles were determined in etiolated and de-etiolated branches of the avocado rootstock VC801. Differences in chlorophyll content and tissue rigidity, and changes in xyloglucan and pectin in cambium and parenchyma cells were found. Interestingly, lignin and sugar contents were similar, suggesting that de-etiolated branches resemble the etiolated ones in this respect. Surprisingly, the branches that underwent short de-etiolation rooted better than the etiolated ones, and only a slight difference in IAA content between the two was observed. Gene-expression profiles revealed an increase in ethylene-responsive transcripts in the etiolated branches, which correlated with enrichment in xyloglucan hydrolases. In contrast, transcripts encoding pectin methylesterase and pectolyases were enriched in the de-etiolated branches. Taken together, it seems that the short de-etiolation period led to fine tuning of the conditions favoring adventitious root formation in terms of auxin–ethylene balance and cell-wall properties.

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