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Proteomic Characterisation of Pateamine A Treatment of Glioblastoma

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thesis
posted on 06.08.2022, 01:20 authored by Pot, Veronica

Pateamine A is a potent inhibitor of eukaryotic translation initiation factor eIF4A, with potential application in cancer treatment. Glioblastoma is a highly aggressive and clinically challenging type of brain cancer. Existing evidence shows glioblastoma exhibit an abnormal energy metabolism, and there is also evidence that pateamine A causes alterations in the energy metabolism of other cancer cell lines. This research investigates the effects of eIF4A inhibition on biological pathways in glioblastoma cells, via pro- teomic analysis and gene ontology analysis. Characterising changes in the proteome as a result of pateamine inhibition of eIF4A contributes to the understanding of pre-initiation influences on mRNA processing, and elucidates alterations in glioblastoma metabolism following pateamine A treatment.

An elongation inhibitor, cycloheximide, was used as a control, as was a human leukaemia cell line. The two glioblastoma cell lines, LN18 and U87, exhibited direct effects on translation ontologies as a result of cyclohex- imide treatment. When compared to translational inhibition, pateamine A treatment caused alterations in RNA transcription splicing in glioblastoma. Other effects were also seen in ribosomal biogenesis and mitochondrial translation. This research characterised proteomic effects of pateamine A and cycloheximide treatment on two glioblastoma cell lines, and evidenced alterations in a range of cell processes.

History

Copyright Date

06/08/2022

Date of Award

06/08/2022

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

CC BY-SA 4.0

Degree Discipline

Biology

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Masters

Degree Name

Master of Drug Discovery and Development

Victoria University of Wellington Unit

Ferrier Research Institute

ANZSRC Socio-Economic Outcome code

280102 Expanding knowledge in the biological sciences

ANZSRC Type Of Activity code

4 Experimental research

Victoria University of Wellington Item Type

Awarded Research Masters Thesis

Language

en_NZ

Victoria University of Wellington School

School of Biological Sciences

Advisors

Teesdale-Spittle, Paul