scholarly journals Wilms Tumor–Associated ENL Mutants Cause Target-Gene Overexpression

2020 ◽  
Vol 10 (2) ◽  
pp. 174.2-174
2021 ◽  
Author(s):  
Madhab Kumar Sen ◽  
Katerina Hamouzová ◽  
Jakub Mikulka ◽  
Rohit Bharati ◽  
Pavlina Košnarová ◽  
...  

2014 ◽  
Vol 289 (35) ◽  
pp. 24452-24462 ◽  
Author(s):  
Karin M. Kirschner ◽  
Julian F.W. Braun ◽  
Charlotte L. Jacobi ◽  
Lucas J. Rudigier ◽  
Anja Bondke Persson ◽  
...  

2017 ◽  
Vol 482 (4) ◽  
pp. 802-807 ◽  
Author(s):  
Tove Ullmark ◽  
Giorgia Montano ◽  
Linnea Järvstråt ◽  
Helena Jernmark Nilsson ◽  
Erik Håkansson ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 87136-87150 ◽  
Author(s):  
Helena Jernmark Nilsson ◽  
Giorgia Montano ◽  
Tove Ullmark ◽  
Andreas Lennartsson ◽  
Kristina Drott ◽  
...  

2021 ◽  
Author(s):  
Carlos Barajas ◽  
Jesse Gibson ◽  
Luis Sandoval ◽  
Domitilla Del Vecchio

AbstractOverexpression of synthetic genes depletes cellular resources, particularly ribosomes, which leads to lower expression of other synthetic genes and decreased growth rate. These burden effects can be detrimental to genetic circuit performance and hinders the process of modularly composing genetic circuits to create complex biomolecular systems with novel functions. No solution exists that allows the expression of any gene to a desired level without hindering the expression level of all other genes and growth rate. Here, we engineer an actuator that upregulates ribosome production. The key component of the actuator is a genetic cassette that expresses the hydrolysis domain of the SpoT enzyme (SpoTH) in a cell strain with elevated basal levels of ppGpp. We demonstrate that our actuator is capable of increasing protein production rates (proxy for free ribosomes) by over 150% and growth rate by over 80%. We use the actuator to engineer a feedforward controller, in which SpoTH is co-expressed with a target gene. Expressing the target gene without SpoTH purges the expression of a constitutive gene by more than 80% and cellular growth rate by 40%. By contrast, with SPOTH, the feedforward controller can be tuned to guarantee less than 10% change in the expression of a constitutive gene while keeping the expression of a the target gene at any desired level without any decrease in growth rate (however growth can increase by ≈40%). Alternatively, the feedforward controller can be tuned to guarantee less than 10% deviations in growth rate while also providing 30% higher expression of a constitutive gene relative to the case of expressing the target gene without SpoTH. Therefore, this solution allows desired target gene overexpression without burden, which is instrumental for predictable composition of genetic circuits.


2004 ◽  
Vol 279 (32) ◽  
pp. 33575-33585 ◽  
Author(s):  
Patricia Stanhope-Baker ◽  
Patricia M. Kessler ◽  
Wenliang Li ◽  
Munna L. Agarwal ◽  
Bryan R. G. Williams

2010 ◽  
Vol 285 (19) ◽  
pp. 14585-14593 ◽  
Author(s):  
Myoung Shin Kim ◽  
Seung Kew Yoon ◽  
Frank Bollig ◽  
Jirouta Kitagaki ◽  
Wonhee Hur ◽  
...  

2020 ◽  
Author(s):  
Basavaraj Vastrad ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti

Abstract Wilms tumor (WT) is a childhood kidney cancer with unknown etiology. Gene expression analysis has become very essential in WT. Thus, we performed an integrated analysis of gene expression data to identify new molecular mechanisms and key functional genes in WT. Gene expression (GSE60850) dataset was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using limma. Pathway and Gene Ontology (GO) enrichment analyses were performed for the DEGs by ToppGene database. Then, protein–protein interaction (PPI) networks and modules were established by the Mentha database and PEWCC1, and visualized by Cytoscape software. Target gene - miRNA regulatory network and target gene - TF regulatory network were established by the Network Analyst database and visualized by Cytoscape software. Finally, survival analysis, expression analysis, stage analysis, mutation analysis, immunohistochemical (IHC) analysis, receiver operating characteristic (ROC), reverse transcription polymerase chain reaction (RT-PCR) and immune infiltration analysis of hub genes was performed. We identified 988 DEGs ultimately including 502 up regulated genes and 486 down regulated genes. Pathway and GO enrichment analysis revealed that DEGs were mainly enriched in D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis, platelet activation, cholesterol biosynthesis III, and complement, coagulation cascades, embryo development, cell surface, DNA-binding transcription factor activity, carboxylic acid metabolic process, extracellular space and signaling receptor binding. FN1, AURKA, TRIM41, NFKBIA, TXNDC5, SIN3A, MAGI1, GPRASP2, UCHL1 and FXYD6 were filtrated as the hub genes. These identified DEGs and hub genes facilitate our knowledge of the underlying molecular mechanism of WT and have the potential to be used as diagnostic and prognostic biomarkers or therapeutic targets for WT.


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