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The N-terminal acetylation (Nta) of proteins is a widespread but poorly understood modification in eukaryotes. Up to 80% of all cytosolic proteins in mammals and plants undergo this modification. It is considered as co-translational and irreversible, in contrast to internal lysine acetylation. Such modifications can have significant influence on protein behavior with respect to protein-protein interaction, subcellular targeting and protein stability, the latter being dependent on the N-end rule pathway of proteolysis via ubiquitination and the proteasome.
Nta is carried out by N-acetyltransferase protein complexes (Nats) that consist of a catalytic subunit and an auxiliary subunit for ribosome interaction. The NatA complex recognizes certain exposed amino acids after excision of the initial methionine, whereas NatB and NatC complexes target initial methionines that precede acidic or hydrophobic residues, respectively.
Despite the massive extent of modification, the functional relevance has remained elusive. Mutants of Nat complex subunits have shown developmental defects in animals, humans and plants, and a new branch of the N-end rule pathway, the Ac/N degron, has been proposed from work in yeasts.
Recent results have shown that the NatA complex is indispensable for embryonic development in Arabidopsis thaliana. After application of drought stress, Nt-acetylation decreased significantly and NatA abundance was rapidly downregulated by the phytohormone abscisic acid. Moreover, lowering of acetylation of NatA targets using a micro RNA approach resulted in extreme drought tolerance due to a constitutive drought stress phenotype.
This PhD project aims at the mechanistic investigation of NatA and NatB function in Arabidopsis thaliana. It is based on the previous findings and it will be further dealing with stress conditions and their effect on Nat interactions and modifications. Next, the impact of the ubiquitin/proteasome system on protein turnover and changes of the acetylome patterns under stress will be investigated. Last but not least, role of Ac/N degrons for degradation of target proteins under stress will be adressed.