Matches in SemOpenAlex for { <https://semopenalex.org/work/W2564656211> ?p ?o ?g. }
Showing items 1 to 69 of
69
with 100 items per page.
- W2564656211 abstract "HIF-1 is a heterodimeric transcription factor comprising HIF-1[alpha] and HIF-1[Beta] subunits. Cellular response to hypoxia relies on the dimerisation of HIF-1? and HIF-1? in the nucleus, forming HIF-1, which then initiates transcription of target genes. Both subunits are constitutively expressed, but the ? subunit is degraded in an oxygen-dependent manner, so it is only stabilised in hypoxia. HIF-1 expression is deregulated in many cancers and has been associated with resistance to chemotherapy. Therefore, understanding the molecular mechanisms of hypoxic response is key to developing cancer therapeutics. This thesis describes the construction and validation of a novel method to study the HIF-1 pathway by reprogramming cellular behaviour. This is achieved by targeting HIF-1[alpha]/HIF-1[Beta] dimerisation with an endogenously expressed molecular inhibitor. The compound, cyclo-CLLFVY, was previously identified through screening of a library of biologically synthesised cyclic peptides. In this study, the peptide sequence was genetically-encoded, between split Nostoc punctiforme DnaE inteins, onto the chromosome of a mammalian cell line, to allow inducible expression and in situ cyclisation of the peptide. The utility of this methodology was demonstrated via identification of genes specifically transactivated by HIF-1 or HIF-2 transcription factors in hypoxia, in the integrated cell line. Furthermore, cell viability assays showed that specific inhibition of HIF-1 dimerisation in these cells increased cellular sensitivity to glucose deprivation and to inhibition of glycolysis. In addition, the epigenetic regulation of HIF-1[alpha] was studied. HIF-1 transactivates the expression of its [alpha]-subunit resulting in positive autoregulation, which contributes to the build up of HIF-1[alpha] at the onset of hypoxia. This autoregulation is dependent on an unmethylated CpG site in the hypoxia response element (HRE) within the promoter of the HIF-1[alpha] gene. Given the key role of HIF-1 in the development of the mammalian embryo, the methylation status of the HIF-1[alpha] HRE in developing tissue was sought. The HIF-1[alpha] HRE was unmethylated in several embryonic tissues, suggesting that transactivation of HIF-1[alpha] plays a role in HIF-1-mediated gene expression during development." @default.
- W2564656211 created "2017-01-06" @default.
- W2564656211 creator A5084275440 @default.
- W2564656211 date "2016-06-23" @default.
- W2564656211 modified "2023-09-27" @default.
- W2564656211 title "Reprogramming the cellular response to hypoxia" @default.
- W2564656211 hasPublicationYear "2016" @default.
- W2564656211 type Work @default.
- W2564656211 sameAs 2564656211 @default.
- W2564656211 citedByCount "0" @default.
- W2564656211 crossrefType "dissertation" @default.
- W2564656211 hasAuthorship W2564656211A5084275440 @default.
- W2564656211 hasConcept C104292427 @default.
- W2564656211 hasConcept C104317684 @default.
- W2564656211 hasConcept C138885662 @default.
- W2564656211 hasConcept C150194340 @default.
- W2564656211 hasConcept C153911025 @default.
- W2564656211 hasConcept C179926584 @default.
- W2564656211 hasConcept C41895202 @default.
- W2564656211 hasConcept C54355233 @default.
- W2564656211 hasConcept C55493867 @default.
- W2564656211 hasConcept C77255625 @default.
- W2564656211 hasConcept C81885089 @default.
- W2564656211 hasConcept C83730767 @default.
- W2564656211 hasConcept C86339819 @default.
- W2564656211 hasConcept C86803240 @default.
- W2564656211 hasConcept C95444343 @default.
- W2564656211 hasConceptScore W2564656211C104292427 @default.
- W2564656211 hasConceptScore W2564656211C104317684 @default.
- W2564656211 hasConceptScore W2564656211C138885662 @default.
- W2564656211 hasConceptScore W2564656211C150194340 @default.
- W2564656211 hasConceptScore W2564656211C153911025 @default.
- W2564656211 hasConceptScore W2564656211C179926584 @default.
- W2564656211 hasConceptScore W2564656211C41895202 @default.
- W2564656211 hasConceptScore W2564656211C54355233 @default.
- W2564656211 hasConceptScore W2564656211C55493867 @default.
- W2564656211 hasConceptScore W2564656211C77255625 @default.
- W2564656211 hasConceptScore W2564656211C81885089 @default.
- W2564656211 hasConceptScore W2564656211C83730767 @default.
- W2564656211 hasConceptScore W2564656211C86339819 @default.
- W2564656211 hasConceptScore W2564656211C86803240 @default.
- W2564656211 hasConceptScore W2564656211C95444343 @default.
- W2564656211 hasLocation W25646562111 @default.
- W2564656211 hasOpenAccess W2564656211 @default.
- W2564656211 hasPrimaryLocation W25646562111 @default.
- W2564656211 hasRelatedWork W1586921467 @default.
- W2564656211 hasRelatedWork W1830977580 @default.
- W2564656211 hasRelatedWork W1969530780 @default.
- W2564656211 hasRelatedWork W1989953864 @default.
- W2564656211 hasRelatedWork W1994290735 @default.
- W2564656211 hasRelatedWork W2006277744 @default.
- W2564656211 hasRelatedWork W2011070950 @default.
- W2564656211 hasRelatedWork W2011076742 @default.
- W2564656211 hasRelatedWork W2024521619 @default.
- W2564656211 hasRelatedWork W2035637318 @default.
- W2564656211 hasRelatedWork W2065705781 @default.
- W2564656211 hasRelatedWork W2071152621 @default.
- W2564656211 hasRelatedWork W2095349653 @default.
- W2564656211 hasRelatedWork W2097601801 @default.
- W2564656211 hasRelatedWork W2101136754 @default.
- W2564656211 hasRelatedWork W2166932492 @default.
- W2564656211 hasRelatedWork W2757554288 @default.
- W2564656211 hasRelatedWork W2900253804 @default.
- W2564656211 hasRelatedWork W2991330371 @default.
- W2564656211 hasRelatedWork W3112375742 @default.
- W2564656211 isParatext "false" @default.
- W2564656211 isRetracted "false" @default.
- W2564656211 magId "2564656211" @default.
- W2564656211 workType "dissertation" @default.