A5035546319- Endoplasmic Reticulum Stress and Disease
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Metabolism and Genetic Disorders
- Polyamine Metabolism and Applications
- Heat shock proteins research
- Animal Genetics and Reproduction
- Sulfur Compounds in Biology
- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Viral Infections and Immunology Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Muscle metabolism and nutrition
Case Western Reserve University
2016-2025
University School
2004-2024
Human Genome Sciences (United States)
2020
Western University of Health Sciences
2008-2015
Institute of Pharmacology
2014
Indiana University School of Medicine
2013
Kyushu University
2004
Jewish General Hospital
2004
McGill University
2004
Wake Forest University
2004
Adaptation to changes in extracellular tonicity is essential for cell survival. However, severe or chronic hyperosmotic stress induces apoptosis, which involves cytochrome c (Cyt c) release from mitochondria and subsequent apoptosome formation. Here, we show that angiogenin-induced accumulation of tRNA halves (or tiRNAs) accompanied by increased survival hyperosmotically stressed mouse embryonic fibroblasts. Treatment cells with angiogenin inhibits stress-induced formation the increases...
Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making more dependent on glutamine. Compared with isogenic wild-type (WT) mutant CRCs convert substantially to α-ketoglutarate replenish the tricarboxylic acid cycle and generate ATP. Mutant p110α upregulates GPT2 gene expression through an...
The tumor suppressor p53, a sensor of multiple forms cellular stress, is regulated by post-translational mechanisms to induce cell-cycle arrest, senescence, or apoptosis. We demonstrate that endoplasmic reticulum (ER) stress inhibits p53-mediated mechanism inhibition involves the increased cytoplasmic localization p53 due phosphorylation at serine 315 and 376, which mediated glycogen synthase kinase-3 β (GSK-3β). ER induces GSK-3β binding in nucleus enhances suppressor. Inhibition apoptosis...
Certain stress conditions can induce cleavage of tRNAs around the anticodon loop via use ribonuclease angiogenin. The cellular factors that regulate tRNA are not well known. In this study we used normal and eIF2α phosphorylation-deficient mouse embryonic fibroblasts applied a microarray-based methodology to identify compare patterns in response hypertonic stress, oxidative (arsenite), treatment with recombinant all three scenarios deficient phosphorylation showed higher accumulation...
Initiation of translation from most cellular mRNAs occurs via scanning; the 40 S ribosomal subunit binds to m<sup>7</sup>G-cap and then moves along mRNA until an initiation codon is encountered. Some contain internal ribosome entry sequences (IRESs) within their 5′-untranslated regions, which allow independently 5′-cap. This study investigated ability stress regulate activity IRESs in mRNAs. Three stresses were studied that cause phosphorylation factor, eIF2α, by activating specific kinases:...
The sulfhydration of cysteine residues in proteins is an important mechanism involved diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes sulfhydrated cysteines systems. Bioinformatics analysis revealed that are part wide range functions. In pancreatic β cells exposed endoplasmic reticulum (ER) stress, elevated H2S promotes enzymes energy metabolism and stimulates glycolytic flux. propose transcriptional translational reprogramming by...
The cancer epigenome exhibits global loss of DNA methylation, which contributes to genomic instability and aberrant gene expression by mechanisms that are yet be fully elucidated. We previously discovered over 3300 long non-coding (lnc)RNAs in human cells demonstrated specific lncRNAs regulate via interactions with chromatin-modifying complexes. Here, we tested whether could also associate methyltransferases methylation expression. Using RIP-seq, identified a subset interact the...
The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) causes stress to which an unfolded protein response is activated render cell survival or apoptosis (chronic stress). Transcriptional and translational reprogramming tightly regulated during ensure specific gene expression. master regulator this PERK/eIF2α/ATF4 signaling where eIF2α phosphorylated (eIF2α-P) by kinase PERK. This signal leads global shutdown, but it also enables translation transcription factor...
Endoplasmic reticulum (ER) stress-induced responses are associated with the loss of insulin-producing β-cells in type 2 diabetes mellitus. β-Cell survival during ER stress is believed to depend on decreased protein synthesis rates that mediated via phosphorylation translation initiation factor eIF2α. It reported here chronic correlated increased islet and apoptosis vivo. Paradoxically, induced an anabolic transcription program overcome translational repression by eIF2α phosphorylation. This...
Abstract Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast NANOG , SNAIL NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), translation subset these stimulated under hypoxia. The accumulation the corresponding proteins induces plasticity “fate-switching” toward stem cell-like phenotypes....
Upon mitochondrial dysfunction, CHOP acts as a rheostat that attenuates prolonged stress and delays the onset of cardiomyopathy.
Abstract Pancreatic β-cells are prone to endoplasmic reticulum (ER) stress due their role in insulin secretion. They require sustainable and efficient adaptive responses cope with this stress. Whether episodes of chronic directly compromise β-cell identity is unknown. We show here under reversible, conditions undergo transcriptional translational reprogramming associated impaired expression regulators function identity. Upon recovery from stress, regain function, indicating a high degree...
During the progression of type 1 diabetes (T1D), β cells are exposed to significant stress and, therefore, require adaptive responses survive. The mechanisms that can preserve cell function and survival in face autoimmunity remain unclear. Here, we show deletion unfolded protein response (UPR) genes Atf6α or Ire1α non-obese diabetic (NOD) mice prior insulitis generates a p21-driven early senescence phenotype alters secretome significantly enhances leukemia inhibitory factor-mediated...
Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4's induction under was thought to be due delayed translation reinitiation, where reinitiation-permissive upstream open reading frame 1 (uORF1) plays key role. Accumulating evidence challenging this mechanism as sole source ATF4 control prompted us investigate additional regulatory routes. We identified highly conserved stem-loop in...
The cationic amino acid transporter, Cat-1, facilitates the uptake of essential acids arginine and lysine. Amino starvation causes accumulation increased translation cat-1 mRNA, resulting in a 58-fold increase protein levels uptake. A bicistronic mRNA expression system was used to demonstrate presence an internal ribosomal entry sequence (IRES) within 5'-untranslated region mRNA. This study shows that IRES-mediated is regulated by availability. IRES under conditions starvation. In contrast,...
The copper(II) complex A0 induces a type of non-apoptotic cell death also known as paraptosis. Paraptosis involves extensive endoplasmic reticulum vacuolization in the absence caspase activation. A wide panel human cancer lines was used to demonstrate differences cytotoxicity by paraptosis-inducing drug and metal-based pro-apoptotic cisplatin. Gene expression profiling fibrosarcoma HT1080 cells showed that, while cisplatin induced p53 targets, up-regulated genes involved unfolded protein...