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Effects of hyperthermia and HSP70 protein overexpression on FOXO3a levels in Acute Lymphoblastic T-cells

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dc.contributor.advisor Mosser, Richard
dc.contributor.author Verzijlenberg, Lisette
dc.date.accessioned 2017-09-01T17:47:23Z
dc.date.available 2017-09-01T17:47:23Z
dc.date.copyright 2017-08
dc.date.created 2017-08-23
dc.date.issued 2017-09-01
dc.identifier.uri http://hdl.handle.net/10214/11490
dc.description.abstract Cells that are damaged by hyperthermia are eliminated by apoptosis. Forkhead Box O3a (FoxO3a) is a transcription factor that triggers transcription of pro-apoptotic genes facilitating cell death. Normally FOXO3a associates with 14-3-3 proteins in the cytoplasm and is ubiquitinated and degraded by the proteasome. Turnover of FOXO3a is regulated by Akt-mediated phosphorylation at residues T32, S253, and S315. Dephosphorylation leads to nuclear translocation and transcriptional activation of the apoptotic program. Stress activates an evolutionarily conserved ‘heat shock response’ producing heat-shock proteins like HSP70, which act as a defence mechanism limiting protein damage and thereby allowing survival of cells exposed to proteotoxic stress. We demonstrated that hyperthermia causes nuclear translocation of FOXO3a which is inhibited in cells expressing HSP70. Additionally, hyperthermia targeted FOXO3a for proteasomal and caspase mediated degradation. Together, these results suggest a mechanism where HSP70 protects cells from cell stress by preventing the nuclear accumulation of FOXO3a and accelerating its destruction. en_US
dc.language.iso en en_US
dc.subject HSP70 en_US
dc.subject FOXO3a en_US
dc.subject stress en_US
dc.subject apoptosis en_US
dc.title Effects of hyperthermia and HSP70 protein overexpression on FOXO3a levels in Acute Lymphoblastic T-cells en_US
dc.type Article en_US
dc.degree.programme Molecular and Cellular Biology en_US
dc.degree.name Master of Science en_US
dc.degree.department Department of Molecular and Cellular Biology en_US


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