scholarly journals Novel Factors of Viral Origin Inhibit TOR Pathway Gene Expression

2018 ◽  
Vol 9 ◽  
Author(s):  
Rosanna Salvia ◽  
Marisa Nardiello ◽  
Carmen Scieuzo ◽  
Andrea Scala ◽  
Sabino A. Bufo ◽  
...  
2017 ◽  
Vol 16 ◽  
pp. 117693511774013 ◽  
Author(s):  
Hien H Nguyen ◽  
Susan C Tilton ◽  
Christopher J Kemp ◽  
Mingzhou Song

The mechanistic basis by which the level of p27Kip1 expression influences tumor aggressiveness and patient mortality remains unclear. To elucidate the competing tumor-suppressing and oncogenic effects of p27Kip1 on gene expression in tumors, we analyzed the transcriptomes of squamous cell papilloma derived from Cdkn1b nullizygous, heterozygous, and wild-type mice. We developed a novel functional pathway analysis method capable of testing directional and nonmonotonic dose response. This analysis can reveal potential causal relationships that might have been missed by other nondirectional pathway analysis methods. Applying this method to capture dose-response curves in papilloma gene expression data, we show that several known cancer pathways are dominated by low-high-low gene expression responses to increasing p27 gene doses. The oncogene cyclin D1, whose expression is elevated at an intermediate p27 dose, is the most responsive gene shared by these cancer pathways. Therefore, intermediate levels of p27 may promote cellular processes favoring tumorigenesis—strikingly consistent with the dominance of heterozygous mutations in CDKN1B seen in human cancers. Our findings shed new light on regulatory mechanisms for both pro- and anti-tumorigenic roles of p27Kip1. Functional pathway dose-response analysis provides a unique opportunity to uncover nonmonotonic patterns in biological systems.


2011 ◽  
Vol 14 (10) ◽  
pp. 1107-1117 ◽  
Author(s):  
Mehmet Turktekin ◽  
Ece Konac ◽  
H. Ilke Onen ◽  
Ebru Alp ◽  
Akin Yilmaz ◽  
...  

2017 ◽  
Vol 162 (1) ◽  
pp. 191-198 ◽  
Author(s):  
Rajesh Ramanathan ◽  
Amy L. Olex ◽  
Mikhail Dozmorov ◽  
Harry D. Bear ◽  
Leopoldo Jose Fernandez ◽  
...  

2003 ◽  
Vol 23 (2) ◽  
pp. 629-635 ◽  
Author(s):  
John R. Rohde ◽  
Maria E. Cardenas

ABSTRACT The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1 from RP gene promoters and leads to histone H4 deacetylation without affecting promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies Rpd3 as the major histone deacetylase responsible for reversing histone H4 acetylation at RP gene promoters in response to Tor inhibition by rapamycin or nutrient limitation. Our results illustrate that the Tor pathway links nutrient sensing with histone acetylation to control RP gene expression and cell growth.


Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 37-49 ◽  
Author(s):  
J.N. Maloof ◽  
J. Whangbo ◽  
J.M. Harris ◽  
G.D. Jongeward ◽  
C. Kenyon

The specification of body pattern along the anteroposterior (A/P) body axis is achieved largely by the actions of conserved clusters of Hox genes. Limiting expression of these genes to localized regional domains and controlling the precise patterns of expression within those domains is critically important for normal patterning. Here we report that egl-20, a C. elegans gene required to activate expression of the Hox gene mab-5 in the migratory neuroblast QL, encodes a member of the Wnt family of secreted glycoproteins. We have found that a second Wnt pathway gene, bar-1, which encodes a beta-catenin/Armadillo-like protein, is also required for activation of mab-5 expression in QL. In addition, we describe the gene pry-1, which is required to limit expression of the Hox genes lin-39, mab-5 and egl-5 to their correct local domains. We find that egl-20, pry-1 and bar-1 all function in a linear genetic pathway with conserved Wnt signaling components, suggesting that a conserved Wnt pathway activates expression of mab-5 in the migratory neuroblast QL. Moreover, we find that members of this Wnt signaling system play a major role in both the general and fine-scale control of Hox gene expression in other cell types along the A/P axis.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Breann Abernathy ◽  
Ran Blekhman ◽  
Tonya Schoenfuss ◽  
Daniel Gallaher

Abstract Objectives We investigated the intersection between the gut microbiome and gene expression of colon and liver tissues in rats, using prebiotic dietary fibers to modulate the gut microbiome and elicit health benefits to the host. Methods Male Wistar rats were fed normal fat (NF) or high fat (HF, 51% fat by kcal) diets containing various fibers (6% fiber + 3% cellulose, by weight); including cellulose (NFC and HFC, non-fermentable), polylactose (HFPL, a novel prebiotic), and polydextrose (HFPD, an established prebiotic). After 10 weeks, tissues were harvested. Transcriptome analysis was performed by RNA sequencing of colon and liver tissues, and cecal contents were utilized for 16S microbiome sequencing. Analyses were conducted in R using DESeq2, DADA2, and phyloseq. Results Analysis of the gut microbiome revealed an increased abundance of probiotic genera, Bifidobacterium and Lactobacillus, in HFPL fed animals when compared to all other groups. These species are galactose fermenters which synthesize short chain fatty acids (SCFAs). This increased taxonomical abundance correlated with an increased FFar3 (SCFA receptor) expression in the colon. This suggests increased FFar3 signaling, leading to increased energy expenditure and GLP-1 and PYY secretion. Additionally, HFPL and HFPD groups had a decreased Firmicutes: Bacteroidetes ratio, which is associated with reduced adiposity due to the Bacteroidetes phylum being poor carbohydrate metabolizers, resulting in reduced energy uptake, yet increased SCFA synthesis. Bacteriodetes are also able to survive in SCFA and bile acid rich environments and are involved in the recycling of bile acids which negatively regulates cholesterol synthesis. This corresponds to reduced liver cholesterol and cholesterol synthesis pathway expression in the HFPL group. Further, liver gene expression revealed reduced lipid synthesis and increased lipid oxidation pathway gene expression in the HFPL group, corresponding to the reduction in fatty liver found in this group. Conclusions Prebiotic dietary fibers elicit changes in the gut microbiome and gene expression in liver and colon. Changes in gene expression correlated with the abundance of beneficial gut bacteria, providing a connection between the gut microbiome and health benefits to the host. Funding Sources Midwest Dairy Association. Supporting Tables, Images and/or Graphs


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