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

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dc.contributor.authorField, Jared
dc.contributor.examiningcommitteeWhyard, Steve (Biological Sciences) West, Adrian (Physiology and Pathophysiology)en_US
dc.contributor.supervisorDiehl-Jones, William (Biological Sciences) Gordon, Joseph (Nursing)en_US
dc.date.accessioned2018-01-18T20:45:28Z
dc.date.available2018-01-18T20:45:28Z
dc.date.issued2017
dc.degree.disciplineBiological Sciencesen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractThe 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.description.noteFebruary 2018en_US
dc.identifier.urihttp://hdl.handle.net/1993/32858
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectCell biologyen_US
dc.subjectCell deathen_US
dc.subjectBnip3 splicingen_US
dc.subjectCalcium signallingen_US
dc.titleAlternative splicing of Bnip3 modulates calcium signals to prevent mitochondrial-dependent cell death and regulate gene expression.en_US
dc.typemaster thesisen_US
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