2018-09-20
Dynamics of Protein Ubiquitination upon Proteasome Modulation : A Quantitative Mass Spectrometry Approach
Publication
Publication
Dynamiek van eiwit ubiquitinatie als gevolg van proteasoom modulatie : Onderzocht door middel van kwantitatieve massaspectrometrie
Scope of the Thesis
The proteasome is a protein complex mostly known for its role in the degradation of unneeded,
damaged or misfolded proteins. The proteasome plays a central role in all cells and hence a
widely studied protein assembly. Malfunctioning of this protein complex has major effects on
cellular processes and is known to lead to the development of a variety of diseases such as cancer
and neurodegenerative disorders. The proteasome is also an important target for drug discovery;
for instance, proteasome inhibitors are used for the treatment of multiple myeloma. However,
not much is known about the biological mechanisms behind these treatments. In this project we
monitored the cellular responses in terms of protein abundance and protein ubiquitination
dynamics upon proteasome malfunctioning (Chapter 3). In order to gain more insight into the
specificity and function of individual proteasome complex components, we also manipulated
single proteasome subunits, i.e., the proteasome-bound deubiquitinating enzymes (DUBs) and
monitored the effects on the cellular (modified) proteome (Chapter 4). The proteasome is a key
player in maintaining a balance in proteostasis under both normal and abnormal cellular
conditions. In order to gain further knowledge about the functioning of the proteasome under
such conditions we characterized the proteasome interactome under different stress conditions,
such as oxidative stress, endoplasmatic reticulum stress and proteasome inhibition (Chapter 5).
Large scale quantitative mass spectrometry is the central methodology applied in all studies
described in this thesis. These types of global and unbiased approaches make it possible to study
the relation of a protein complex with its direct cellular protein environment. In Chapter 6 we
have monitored changes in the cellular environment upon activation of ecdysone-responsive
genes, in terms of global transcriptome and global proteome dynamics, as well as in terms of
ecdysone-receptor interactome dynamics. As such, this work provides several clues to address
the relationship between mRNA and protein abundances in Drosophila.
Additional Metadata | |
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, , , , , | |
C.P. Verrijzer (Peter) , J.A.A. Demmers (Jeroen) | |
Erasmus University Rotterdam | |
hdl.handle.net/1765/110280 | |
Organisation | Proteomics Center |
Sap, K. (2018, September 20). Dynamics of Protein Ubiquitination upon Proteasome Modulation : A Quantitative Mass Spectrometry Approach. Retrieved from http://hdl.handle.net/1765/110280 |
Additional Files | |
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Cover-image-Sap.PNG Cover Image , 42kb | |
1_title_pages_KSap.pdf Final Version , 189kb | |
2_ch1_KSap.pdf Final Version , 1mb | |
3_scope_KSap.pdf Final Version , 132kb | |
4_ch2_KSap.pdf Final Version , 1mb | |
5_ch3_KSap.pdf Final Version , 2mb | |
6_ch4_KSap.pdf Final Version , 4mb | |
7_ch5_KSap.pdf Final Version , 4mb | |
8_ch6_KSap.pdf Final Version , 1mb | |
9_ch7_KSap.pdf Final Version , 349kb | |
10_appendix_KSap.pdf Final Version , 194kb | |
11_dankwoord_KSap_permanent_embargo.pdf Final Version , 119kb | |
_propositions_KSap.pdf , 55kb |