A5017117277- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA regulation and disease
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
- RNA Interference and Gene Delivery
- Molecular Biology Techniques and Applications
- Plant pathogens and resistance mechanisms
- HIV/AIDS drug development and treatment
- Autophagy in Disease and Therapy
- Nitrogen and Sulfur Effects on Brassica
- Plant biochemistry and biosynthesis
- Biopolymer Synthesis and Applications
- Immune Cell Function and Interaction
- Microbial Natural Products and Biosynthesis
- Viral Infections and Immunology Research
- Polyamine Metabolism and Applications
- Escherichia coli research studies
- 3D Printing in Biomedical Research
- Plant Pathogens and Fungal Diseases
- Wheat and Barley Genetics and Pathology
- Cancer-related molecular mechanisms research
- Genomics, phytochemicals, and oxidative stress
- Mycotoxins in Agriculture and Food
University of Lethbridge
2016-2024
University of Calgary
2018-2024
Cancer Institute (WIA)
2018
Children's Hospital of Eastern Ontario
2009-2016
Hôpital d'Enfants
2009
Nrf2 plays pivotal roles in coordinating the antioxidant response and maintaining redox homeostasis. expression is exquisitely regulated; suppressed under unstressed conditions but strikingly induced oxidative stress. Previous studies showed that stress-induced up-regulation results from both inhibition of degradation enhanced translation. In present study, we elucidate mechanism underlying translational control Nrf2. An internal ribosomal entry site (IRES) was identified within 5′...
Physiological and pathophysiological stress attenuates global translation via phosphorylation of eIF2α. This in turn leads to the reprogramming gene expression that is required for adaptive response. One class cellular messenger RNAs whose was reported be insensitive eIF2α phosphorylation-mediated repression harboring an Internal Ribosome Entry Site (IRES). IRES-mediated several apoptosis-regulating genes increases response hypoxia, serum deprivation or gamma irradiation promotes tumor cell...
Apoptosis can be regulated by extracellular signals that are communicated peptides such as fibroblast growth factor 2 (FGF-2) have important roles in tumor cell proliferation. The prosurvival effects of FGF-2 transduced the activation ribosomal protein S6 kinase (S6K2), which increases expression antiapoptotic proteins X chromosome-linked Inhibitor (XIAP) and Bcl-x(L). We now show FGF-2-S6K2 signaling is mediated suppressor programmed death 4 (PDCD4). demonstrate PDCD4 specifically binds to...
IRES-mediated translation of key cell fate regulating genes has been implicated in tumorigenesis. Concerted action canonical eukaryotic initiation factors and IRES transacting (ITAFs) was shown to regulate cellular mediated translation; however, the precise molecular mechanism ribosome recruitment IRESes remains unclear. Here we show that X-linked inhibitor apoptosis (XIAP) operates an evolutionary conserved viral like mode structural integrity, particularly vicinity AUG, is critical for...
Abstract Physiological stress conditions attenuate global mRNA translation via modifications of key eukaryotic initiation factors. However, non-canonical mechanisms allow cap-independent certain mRNAs. We have previously demonstrated that eIF5B promotes the encoding antiapoptotic factor, XIAP, during cellular stress. Here, we show depletion sensitizes glioblastoma multiforme cells to TRAIL-induced apoptosis by a pathway involving caspases-8, −9, and −7, with no significant effect on cell...
The functional importance of many non-coding RNAs (ncRNAs) generated by repetitive elements and their connection with pathologic processes remains elusive. B2 RNAs, a class ncRNAs the family SINE repeats, mediate through processing transcriptional activation various genes in response to stress. Here, we show that this is dysfunctional during amyloid beta toxicity pathology mouse hippocampus due increased levels RNA processing, leading constitutively elevated target gene expression high Trp53...
A variety of cellular stresses lead to global translation attenuation due phosphorylation the alpha subunit eukaryotic initiation factor 2 (eIF2), which decreases availability eIF2-GTP-Met-tRNAi ternary complex. However, a subset mRNAs continues be translated by non-canonical mechanisms under these conditions. In fact, although activating transcription 4 (ATF4) is normally repressed an upstream open reading frame (uORF), decreased complex leads increased main ATF4-coding ORF. We show here...
Genetic studies have shown that the MAP kinase MGV1 and transcriptional regulator TRI6 regulate many of same biosynthetic gene clusters (BGCs) in
Glioblastoma multiforme (GBM) is among the deadliest cancers, owing in part to complex inter- and intra-tumor heterogeneity presence of a population stem-like cells called brain tumour stem (BTSCs/BTICs). These cancer survive treatment confer resistance current therapies — namely, radiation chemotherapeutic, temozolomide (TMZ). TMZ induces cell death by alkylating DNA, BTSCs resist this mechanism via robust DNA damage response. Hence, recent studies aimed sensitize using combination therapy,...
During the integrated stress response (ISR), global translation initiation is attenuated; however, noncanonical mechanisms allow for continued of specific transcripts. Eukaryotic factor 5B (eIF5B) has been shown to play a critical role in canonical as well involving internal ribosome entry site (IRES) and upstream open reading frame (uORF) elements. The uORF-mediated regulation activating transcription 4 (ATF4) mRNA plays pivotal cellular ISR. Our recent study confirmed that eIF5B depletion...
Abstract Programmed cell death 4 (PDCD4) protein is a well-characterized tumor suppressor protein. PDCD4 inhibits mRNA translation by inhibiting the activity of an RNA helicase, eukaryotic initiation factor 4A (eIF4A). We have previously reported that interacts with internal ribosome entry site (IRES) element found within 5’ untranslated region (UTR) encoding B-cell lymphoma extra-large (Bcl-xL) PDCD4’s interaction Bcl-xL IRES IRES-mediated on mRNA. However, S6 kinase (S6K)-mediated...
Increasing evidence of sperm RNA's role in fertilization and embryonic development has provided impetus for its isolation thorough characterization. Sperm are considered tough-to-lyse cells due to the compact condensed DNA heads. Lack consensus among bovine RNA protocols introduces experimental variability transcriptome studies. Here, we describe an optimized method total from using TRIzol reagent. This study critically investigated effects various lysis conditions on isolation. suspended...
Translation initiation is the rate-limiting step of protein synthesis and represents a key point at which cells regulate their output. Regulation to cellular stress-response, dysregulation central many disease states, such as cancer. For instance, although stress leads inhibition global translation by attenuating cap-dependent initiation, certain stress-response proteins are selectively translated in cap-independent manner. Discreet RNA regulatory elements, internal ribosome entry sites...