title: Analyzing the individual contributions of translation  initiation factors to shaping the proteome of cancer cells
creator: Bortecen, Toman Deniz
subject: ddc-570
subject: 570 Life sciences
description: In living cells, proteins are synthesized through the complex multi-step process process  of mRNA translation. The initiation step of translation is believed to be rate limiting step  of the process and is subject to diverse regulatory mechanisms. A network of proteins,  referred to as (eukaryotic) translation initiation factors (eIF), facilitate the recruitment and  activation of the translation machinery to initiate protein synthesis. Individual eIF and protein  synthesis in general are frequently deregulated in various human cancers to enable aberrant  cellular growth and proliferation. Increasing evidence suggests that individual eIF proteins  regulate the translation of specific mRNA and do not simply contribute to protein synthesis  globally. Changes in protein synthesis are frequently studied using mRNA sequencing-  based approaches, however, direct measurements of newly synthesized proteins can be  advantageous. However, the majority of established proteomic methods for analyzing  changes in protein synthesis have severe limitations.  In this thesis, a new proteomics workflow was developed to simplify and improve the analysis  of changes in the newly synthesized proteome across numerous conditions. This workflow  was then employed to carry out a systematic analysis of changes in protein synthesis,  induced by the depletion of 40 different eIF proteins in a human cancer cell line model.  The analysis demonstrated that depletion of different eIF lead to distinct changes in protein  synthesis, suggesting that several eIF regulate widespread preferential mRNA translation.  Acquired data and findings from the research conducted in this thesis could potentially help  to characterize specific signatures of eIF-mediated preferential translation of specific mRNA,  which could aid in the development of novel therapeutic strategies.  In summary, this thesis describes an optimized proteomics workflow for the analysis of  newly synthesized proteins was developed and employed to carry out a systematic analysis  of how individual eIF shape the proteome of cancer cells.
date: 2024
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/34859/1/PhD_thesis_TB.pdf
identifier: DOI:10.11588/heidok.00034859
identifier: urn:nbn:de:bsz:16-heidok-348590
identifier:   Bortecen, Toman Deniz  (2024) Analyzing the individual contributions of translation initiation factors to shaping the proteome of cancer cells.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/34859/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng