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NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation

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dc.contributor.author Van Damme, Petra eng
dc.contributor.author Hole, Kristine eng
dc.contributor.author Pimenta-Marques, Ana eng
dc.contributor.author Helsens, Kenny eng
dc.contributor.author Vandekerckhove, Joël eng
dc.contributor.author Martinho, Rui G. eng
dc.contributor.author Gevaert, Kris eng
dc.contributor.author Arnesen, Thomas eng
dc.date.accessioned 2012-02-20T13:56:22Z
dc.date.available 2012-02-20T13:56:22Z
dc.date.issued 2011-07-07 eng
dc.identifier.citation PLoS Genetics 7(7): e1002169 en
dc.identifier.issn 1553-7390 eng
dc.identifier.uri http://hdl.handle.net/1956/5624
dc.description.abstract N-terminal acetylation (N-Ac) is a highly abundant eukaryotic protein modification. Proteomics revealed a significant increase in the occurrence of N-Ac from lower to higher eukaryotes, but evidence explaining the underlying molecular mechanism(s) is currently lacking. We first analysed protein N-termini and their acetylation degrees, suggesting that evolution of substrates is not a major cause for the evolutionary shift in N-Ac. Further, we investigated the presence of putative N-terminal acetyltransferases (NATs) in higher eukaryotes. The purified recombinant human and Drosophila homologues of a novel NAT candidate was subjected to in vitro peptide library acetylation assays. This provided evidence for its NAT activity targeting Met-Lys- and other Met-starting protein N-termini, and the enzyme was termed Naa60p and its activity NatF. Its in vivo activity was investigated by ectopically expressing human Naa60p in yeast followed by N-terminal COFRADIC analyses. hNaa60p acetylated distinct Met-starting yeast protein N-termini and increased general acetylation levels, thereby altering yeast in vivo acetylation patterns towards those of higher eukaryotes. Further, its activity in human cells was verified by overexpression and knockdown of hNAA60 followed by N-terminal COFRADIC. NatF’s cellular impact was demonstrated in Drosophila cells where NAA60 knockdown induced chromosomal segregation defects. In summary, our study revealed a novel major protein modifier contributing to the evolution of N-Ac, redundancy among NATs, and an essential regulator of normal chromosome segregation. With the characterization of NatF, the co-translational N-Ac machinery appears complete since all the major substrate groups in eukaryotes are accounted for. en
dc.language.iso eng eng
dc.publisher Public Library of Science eng
dc.rights Attribution CC BY eng
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ eng
dc.title NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation eng
dc.type Peer reviewed eng
dc.type Journal article eng
dc.subject.nsi VDP::Mathematics and natural science: 400::Basic biosciences: 470::Molecular biology: 473 eng
dc.subject.nsi VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical molecular biology: 711 eng
dc.rights.holder Copyright: 2011 Van Damme et al.
dc.type.version publishedVersion eng
bora.peerreviewed Peer reviewed eng
bibo.doi http://dx.doi.org/10.1371/journal.pgen.1002169 eng
dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1002169


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