A5062068976- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- RNA regulation and disease
- Heat shock proteins research
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Metal complexes synthesis and properties
- Plant Molecular Biology Research
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Fluorescence Microscopy Techniques
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- ATP Synthase and ATPases Research
Royal College of Surgeons in Ireland
2013-2022
Trinity College Dublin
2009
In response to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen, three ER transmembrane signaling proteins, inositol-requiring enzyme 1 (IRE1), PRKR-like kinase (PERK), and activating transcription factor 6α (ATF6α), are activated. These initiate a transcriptional network termed protein (UPR), which re-establishes cellular proteostasis. When this restoration fails, however, cells undergo apoptosis. To investigate cross-talk between these different UPR enzymes,...
The ubiquitin-dependent N-end rule pathway relates the in vivo half-life of a protein to identity its N-terminal residue. This proteolytic system is present all organisms examined and has been shown have multitude functions animals fungi. In plants, however, functional understanding only beginning. hierarchic structure. Destabilizing activity Asp, Glu, (oxidized) Cys requires their conjugation Arg by an arginyl-tRNA-protein transferase (R-transferase). resulting recognized pathway's E3...
Abstract Disturbance of homeostasis within the endoplasmic reticulum ( ER ) lumen leads to accumulation unfolded and misfolded proteins. This results in activation an evolutionary conserved stress response termed that, if unresolved, induces apoptosis. Previously Bcl‐2 homology domain 3‐Only Protein Puma was identified as a mediator stress‐induced apoptosis neurons. In search alternative contributors apoptosis, downregulation anti‐apoptotic family protein Mcl‐1 noted during both mouse...
Abstract There is an ongoing need for the development of new cancer therapeutics that combine high cytotoxic efficiency with low side effects, and also override resistance to first-line chemotherapeutics. Copper(ii)–phenanthroline complexes are promising compounds were shown previously induce immediate response over a panel tumor cell lines in vitro. The molecular mechanism, however, remained unresolved. In this work we performed thorough study copper(ii)–phenanthroline containing different...
The Bcl-2 family proteins BAK and BAX control the crucial step of pore formation in mitochondrial outer membrane during intrinsic apoptosis. Bcl-2-related ovarian killer (BOK) is a protein with high sequence similarity to BAX. However, apoptosis can proceed absence BOK. Unlike BAX, BOK primarily located on endoplasmic reticulum (ER) Golgi membranes, suggesting role for regulating ER homeostasis. In this study, we report that required full stress response. Employing previously characterized...
Targeting the proteasome is a valuable approach for cancer therapy, potentially limited by pro-survival pathways induced in parallel to cell death. Whether these are activated all cells, show different activation kinetics sensitive versus resistant or interact functionally with death unknown. We monitored of heat shock response (HSR), key survival pathway inhibition, relative apoptosis HCT116 colon cells expressing green fluorescent protein (GFP) under control Hsp70 promoter. Single and high...