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Functional regulation of C/EBPbeta through post-translational acetylation

Spoor, Mette (2019) Functional regulation of C/EBPbeta through post-translational acetylation. Master's Internship Report, Biomedical Engineering.

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Abstract

The process of ageing is often accompanied by cancer and metabolic diseases. Members of the CCAAT/enhancer binding protein (C/EBP) family are transcription factors that form an important link between these pathologies, because of their involvement in many cellular processes, such as differentiation, proliferation and metabolism. Lysine (K) acetylation of transcription factors is a potential mechanism of adjusting transcription factor activity and thereby controlling gene regulation. In contrast to C/EBPα acetylation, not much is known about acetylation of C/EBPβ. Therefore, the aim of this project was to identify how C/EBPβ acetylation is regulated and whether acetylation affects C/EBPβ function. The performed experiments showed that all isoforms of C/EBPβ are acetylated when overexpressed. The concomitant overexpression of P/CAF and GCN5 increased acetylation of C/EBPβ, while HDAC1 and HDAC3 decreased acetylation of C/EBPβ. The acetylation mimicking mutation of K239 impaired transcriptional activity of the C/EBPβ isoform LAP, indicating that acetylation of C/EBPβ at K239 decreases the transcriptional activity of LAP. Furthermore, the deacetylation mimicking mutation of K216/217 increased the mitochondrial oxygen consumption rate suggesting that hypoacetylation at K216/217 enhances the function of LAP to stimulate mitochondrial respiration.

Item Type: Thesis (Master's Internship Report)
Supervisor name: Calkhoven, C.F. and Muller, C.
Degree programme: Biomedical Engineering
Thesis type: Master's Internship Report
Language: English
Date Deposited: 14 Jan 2020 10:12
Last Modified: 14 Jan 2020 10:12
URI: https://fse.studenttheses.ub.rug.nl/id/eprint/21389

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