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dc.contributor.authorBrennan, James F.en_US
dc.date.accessioned2015-08-04T18:18:21Z
dc.date.available2015-08-04T18:18:21Z
dc.date.issued2012
dc.date.submitted2012
dc.identifier.other(ALMA)contemp
dc.identifier.urihttps://hdl.handle.net/2144/12294
dc.descriptionThesis (M.A.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.en_US
dc.description.abstractGlycogen synthase kinase-3 (GSK-3) is a regulatory kinase involved in many important mammalian cell functions. The PI 3-kinase/Akt pathway, which is a major regulator of cell growth and survival in proliferating cells, directly inhibits GSK-3. Inhibition of the PI 3-kinase pathway induces expression of cell cycle arrest and pro-apoptotic genes. Some ofthese genes are induced downstream ofGSK-3 signaling. In this study we show that some genes induced following PI 3-kinase inhibition are regulated by transcription factors that are direct targets of GSK-3 regulation. In doing so, we have identified a transcriptional network downstream of GSK-3 signaling that regulates a subset of genes induced by PI 3-kinase inhibition in proliferating cells. In contrast, GSK-3 plays a much different role in cardiomyocytes, a terminally differentiated cell type. GSK-3 activity is known to inhibit the onset of cardiac hypertrophy in cardiomyocytes. When treated with phenylephrine, a hypertrophy inducing agent, cardiomyocytes experience an up-regulation of 131 unique genes as part of the hypertrophic response. Our studies show that direct inhibition of GSK-3 alone is sufficient to significantly up-regulate a subset of genes induced in the hypertrophic response of cardiomyocytes. Furthermore,we show that the transcription factor CREB, which is targeted by GSK-3 , binds and activates genes induced by direct GSK-3 inhibition.en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.titleGene regulation downstream of glycogen synthase kinase-3 in neonatal rat ventricular myocytes and T98G cellsen_US
dc.typeThesis/Dissertationen_US
etd.degree.nameMaster of Artsen_US
etd.degree.levelmastersen_US
etd.degree.disciplineCell and Molecular Biologyen_US
etd.degree.grantorBoston Universityen_US


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