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laura.armbruster AET cos.uni-heidelberg.de
Acetylation is among the most abundant protein modifications in eukaryotes. While 50-70 % of the budding yeast and 70-80 % of the Drosophila proteome are acetylated, more complex organisms such as humans and plants acetylate up to 80-90 % of their proteome. Acetyl moieties can be transferred from acetyl coenzyme A to protein N-termini or ε-amino groups of internal lysine residues. These reactions occur either co- or post-translationally and are catalyzed by various N-terminal (NATs) and lysine acetyltransferases (KATs). While the overall significance of acetylation remains enigmatic, for individual proteins effects of acetylation on protein-protein interaction, subcellular localization, protein turnover and folding, as well as aggregation have been demonstrated.
In plants, the NATs NatA-G have been identified, but their biological significance is mostly unknown. NatA and NatB as ribosome-bound NATs together acetylate more than 75 % of all identified NAT substrates. There are however various NATs with a narrower substrate range and localizations that suggest a post-transcriptional function. NatF for instance is associated with the Golgi membrane whereas the plant specific NatG was found in chloroplast. Sequence homology searches have identified other putative plastidic NATs.
In Arabidopsis thaliana, N-terminal acetylation (NTA) has been shown to be subjected to hormonal control via via abscisic acid. Treatment with the aforementioned phytohormone leads to a downregulation of the NatA subunits NAA10 and NAA15 which in turn results in an accumulation of proteins with free N-termini. Interestingly, mutants of NatA are resistant to drought indicating an essential function of acetylation for coordination of physiological responses to drought stress.
As for lysine acetylation, the modification of histones has been demonstrated to have a central function in regulating defense responses and development in plants. Histone proteins are however not the only known substrates of KATs. Various transcription factors and transcriptional co-regulators are modified by attaching an acetyl moiety to internal lysine residues. Among those are general transcription factors such as TFIIB but also regulators of specific signaling pathways like p53 or NF-κB. Contrary to NTA, lysine acetylation is reversible, so that it may act as a switch to activate and deactivate certain cellular pathways.
My PhD thesis aims to provide a mechanistic understanding of the dynamic regulation of N-terminal and lysine acetylation upon stress in Arabidopsis thaliana. Therefore, I am focusing on the specificities, targets and stress-responsive dynamics of enzymes with dual NAT/KAT activity, especially NatE and the putative plastidic NATs. Moreover, the impact of acetylation on protein turnover and stability will be investigated.