Browsing by Author "Samali, Afshin"
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Bcl-2 family on guard at the ER
Samali, Afshin; Sanjeev, Gupta; Ní Chonghaile, Tríona; MacDonald, David C; Szegezdi, Eva (American Physiological Society, 2009)The endoplasmic reticulum (ER) is the main site for protein folding, lipid biosynthesis and calcium storage in the cell. Disturbances of these critical cellular functions lead to ER stress. The ER responds to disturbances ... -
Cellular responses to endoplasmic reticulum stress: Role of autophagy and cell death
Saveljeva, Svetlana (2014-12-03)This PhD thesis describes cellular responses to the induction of endoplasmic reticulum (ER) stress, focusing on the role of autophagy and cell death. Pro-survival role of unfolded protein response (UPR) is analysed by ... -
Decorated macrocycles via ring-closing double-reductive amination. Identification of an apoptosis inducer of leukemic cells that at least partially antagonizes a 5-HT2 receptor
Zhou, Jian; Reidy, Mairead; O'Reilly, Ciaran; Jarikote, Dilip V.; Negi, Arvind; Samali, Afshin; Szegezdi, Eva; Murphy, Paul V. (American Chemical Society, 2015-03-16)A build-couple-pair strategy, including double-reductive amination macrocyclization, has been used to generate decorated macrocycles (eannaphanes) with an embedded triazole and monosaccharide. Biological screening led to ... -
Decoy Receptors block tumour cell eradication by TRAIL - Molecular engineering of TRAIL to evade decoy receptors
O' Leary, Lynda (2012-06-29)Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a cytokine expressed by immune cells which selectively eradicates a wide range of cancer cells while leaving normal healthy cells unharmed. TRAIL binds ... -
Disruption of microRNA Biogenesis Confers Resistance to ER Stress-Induced Cell Death Upstream of the Mitochondrion
Samali, Afshin (2013)Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown ... -
Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells
Samali, Afshin (2015)Endoplasmic reticulum (ER) stress-induced cellular dysfunction and death is associated with several human diseases. It has been widely reported that ER stress kills through activation of the intrinsic mitochondrial apoptotic ... -
HSP72 Protects Cells from ER Stress-induced Apoptosis via Enhancement of IRE1¿-XBP1 Signaling through a Physical Interaction
Gupta, Sanjeev; Deepti, Ayswaria; Deegan, Shane; Samali, Afshin (2010)Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway ... -
Investigation of IRE1/XBP1s pathway and its potential as a therapeutic target in breast cancer
Cleary, Patricia (2015-09-18)X-Box binding protein 1 (XBP1) is an integral component of the unfolded protein response (UPR), a pro-survival mechanism, triggered by the onset of endoplasmic reticulum stress. Activation of the endoplasmic reticulum ... -
Kinase Inhibitor against Quiescent and Proliferating CLL Cells
Natoni, Alessandro; Murill, Laura S.; Kliszczak, Anna E.; Samali, Afshin; Santocanale, Corrado (2011-07-18)In chronic lymphocytic leukemia (CLL) the proliferation rate and resistance to drug-induced apoptosis are recognized as important factors in the outcome of treatment. In this study, we assess the activity and the mechanism ... -
Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization
Gupta, Sanjeev; Cuffe, Lorraine; Szegezdi, Eva; Logue, Susan E.; Neary, Catherine; Healy, Sandra; Samali, Afshin (2010)During apoptosis, the process of mitochondrial outer membrane permeabilization (MOMP) represents a point-of-no-return as it commits the cell to death. Here we have assessed the role of caspases, Bcl-2 family members and ... -
Methods for Monitoring Endoplasmic Reticulum Stress and the Unfolded Protein Response
Samali, Afshin; FitzGerald, Una; Deegan, Shane; Gupta, Sanjeev (2010)The endoplasmic reticulum (ER) is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and ... -
miRNA signature of unfolded protein response in H9c2 rat cardiomyoblasts
Samali, Afshin (2014)Background: Glucose and oxygen deprivation during ischemia is known to affect the homeostasis of the endoplasmic reticulum (ER) in ways predicted to activate the unfolded protein response (UPR). Activation of UPR signalling ... -
The molecular characterization of ER stress-induced autophagy and cell death
Deegan, Shane (2012-12-21)Autophagy is tightly regulated by the unfolded protein response (UPR). It plays an important role in the removal of unfolded proteins, damaged mitochondria and expanded endoplasmic reticulum (ER), to help relieve ER stress ... -
Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner
Carleton, Laura A; Doyle, Karen M; Samali, Afshin; Gorman, Adrienne; Mnich, Katarzyna; Kavanagh, Edel T (Nature Publishing Group, 2014-05-01)Nerve growth factor (NGF) is well characterised as an important pro-survival factor in neuronal cells that can inhibit apoptotic cell death upstream of mitochondrial outer membrane permeabilisation. Here we addressed the ... -
NGF-induced pro-survivla signalling: Molecular engineering of NGFto enhance pro-survival signalling
Carleton, Laura (2014-01-27)Nerve growth factor (NGF) is a potent pro-survival growth factor that has diverse roles in development and in the adult nervous system. It has two cognate receptors that stimulate distinct signalling pathways, tropomyosin-related ... -
The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis
van Dijk, Marianne; Murphy, Eoin; Morrell, Ruth; O'Dwyer, Michael; Szegezd, Eva; Samali, Afshin (2011)Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents ... -
Rapid and efficient cancer cell killing mediated by high-affinity death receptor homotrimerizing TRAIL variants
Natoni, Alessandro; Szegezdi, Eva; Samali, Afshin (Macmillan Publishers Limited, 2010)The tumour necrosis factor family member TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in a variety of cancer cells through the activation of death receptors 4 (DR4) and 5 (DR5) and is considered ... -
The regulation of ER stress induced cell death by HSPB1 (hsp27)
Kennedy, Donna (2013-01-29)Endoplasmic reticulum (ER) stress is associated with several human pathologies including neurodegenerative disorders. ER stress results in accumulation of unfolded proteins which activates the unfolded protein response ... -
Resistance to TRAIL in non-transformed cells is due to multiple redundant pathways
Samali, Afshin (2013)Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine and a selective inducer of apoptosis in a range of tumour cells, but not in normal, untransformed cells. A large number of chemotherapeutics ... -
The role of microRNAs during endoplasmic reticulum stress induced cell death
Cawley, Karen (2012-04-25)Endoplasmic Reticulum (ER) stress occurs in response to negative insult or stimuli to the cell. It induces a pathway called the unfolded protein response (UPR) which can alleviate stress and restore the cell to its ¿healthy ...