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Alternative splicing of Bnip3 modulates calcium signals to prevent mitochondrial-dependent cell death and regulate gene expression.

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dc.contributor.supervisor Diehl-Jones, William (Biological Sciences) Gordon, Joseph (Nursing) en_US
dc.contributor.author Field, Jared
dc.date.accessioned 2018-01-18T20:45:28Z
dc.date.available 2018-01-18T20:45:28Z
dc.date.issued 2017
dc.identifier.uri http://hdl.handle.net/1993/32858
dc.description.abstract The Bnip3 cell death gene is prominently expressed in many hypoxic-ischemic related pathologies, such as heart failure and necrotising enterocolitis in the intestine. Two isoforms of Bnip3 have been described in the literature: a pro-death full-length protein (Bnip3FL) and a pro-survival protein lacking exon3 (Bnip3∆Ex3). Bnip3∆Ex3 acts as an endogenous inhibitor of Bnip3FL function, yet how Bnip3∆Ex3 serves this function is unknown. In gain-of-function experiments, I use combinations of cell lines and primary cells to dissect the mechanism(s) of Bnip3∆Ex3 action. Herein, I report that Bnip3∆Ex3 expression orchestrates an intricate calcium signalling cascade that has two cellular outcomes. First, calcium signals avert mitochondrially-dependent cell death. Second, these calcium signals modulate transcriptional regulators and gene expression causing morphological cell changes. These data provide original evidence that Bnip3∆Ex3 has the potential to mitigate the detrimental effects of hypoxia and Bnip3FL signalling by activating a complex signalling cascade and multiple survival pathways. en_US
dc.subject Cell biology en_US
dc.subject Cell death en_US
dc.subject Bnip3 splicing en_US
dc.subject Calcium signalling en_US
dc.title Alternative splicing of Bnip3 modulates calcium signals to prevent mitochondrial-dependent cell death and regulate gene expression. en_US
dc.degree.discipline Biological Sciences en_US
dc.contributor.examiningcommittee Whyard, Steve (Biological Sciences) West, Adrian (Physiology and Pathophysiology) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note February 2018 en_US


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