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Towards a functional understanding of protein N-terminal acetylation.

Arnesen T - PLoS Biol. (2011)

Bottom Line: Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic.However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins.These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Bergen, Bergen, Norway. thomas.arnesen@mbi.uib.no

ABSTRACT
Protein N-terminal acetylation is a major modification of eukaryotic proteins. Its functional implications include regulation of protein-protein interactions and targeting to membranes, as demonstrated by studies of a handful of proteins. Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic. However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins. These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

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Functional effects of N-terminal acetylation. 1.Nat complexes associate with ribosomes to perform co-translationalNt-acetylation of a majority of eukaryotic proteins [8]. 2.N-terminal ubiquitination promotes degradation of N-terminally unacetylatedproteins, thus Nt-acetylation may protect proteins from this degradationpathway [15]. 3. The newly discovered N-end rulebranch involves the degradation of Ac-N-degrons via the Doa10 E3 ubiquitinligase [18]. 4. Nt-acetylation is essential for thefunctioning of actin filaments by modulating protein–proteininteractions [21]–[23]. 5. Tfs1requires its acetylated N-terminus to directly inhibit the cytosoliccarboxypeptidase CPY [24]. 6. Nt-acetylation targets theGTPases Arl3p and Grh1p to the Golgi membrane [25]–[27].7. Trm1p-II requires Nt-acetylation for proper associationto the inner nuclear membrane [28]. 8.Nt-acetylated Sir3p specifically interacts with unmethylated lysine 79 ofhistone H3 in silenced chromatin and is essential for proper gene silencing[32]. 9. Nt-acetylation preventspost-translational translocation through the ER membrane [33].
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pbio-1001074-g002: Functional effects of N-terminal acetylation. 1.Nat complexes associate with ribosomes to perform co-translationalNt-acetylation of a majority of eukaryotic proteins [8]. 2.N-terminal ubiquitination promotes degradation of N-terminally unacetylatedproteins, thus Nt-acetylation may protect proteins from this degradationpathway [15]. 3. The newly discovered N-end rulebranch involves the degradation of Ac-N-degrons via the Doa10 E3 ubiquitinligase [18]. 4. Nt-acetylation is essential for thefunctioning of actin filaments by modulating protein–proteininteractions [21]–[23]. 5. Tfs1requires its acetylated N-terminus to directly inhibit the cytosoliccarboxypeptidase CPY [24]. 6. Nt-acetylation targets theGTPases Arl3p and Grh1p to the Golgi membrane [25]–[27].7. Trm1p-II requires Nt-acetylation for proper associationto the inner nuclear membrane [28]. 8.Nt-acetylated Sir3p specifically interacts with unmethylated lysine 79 ofhistone H3 in silenced chromatin and is essential for proper gene silencing[32]. 9. Nt-acetylation preventspost-translational translocation through the ER membrane [33].

Mentions: Unlike most other protein modifications, Nt-acetylation is irreversible; it occursmainly during the synthesis of the protein, catalyzed by N-terminalacetyltransferases (NATs) associated with ribosomes [4]–[7] (Figure 1 and Figure 2, point 1). There are severaldistinct NATs in eukaryotes—NatA‐NatF—each composed of one ormore subunits and each acetylating a specific subgroup of N‐termini dependingon the amino acid sequence of the first few amino acids [8]. The Nt‐acetylationpatterns and the NAT machinery appear to be similar in all organisms from lowereukaryotes like the yeast Saccharomyces cerevisiae to highereukaryotes [1],[9], [10], althoughhigher eukaryotes have more protein Nt‐acetylation and express more NATs thanyeast do [1],[8].


Towards a functional understanding of protein N-terminal acetylation.

Arnesen T - PLoS Biol. (2011)

Functional effects of N-terminal acetylation. 1.Nat complexes associate with ribosomes to perform co-translationalNt-acetylation of a majority of eukaryotic proteins [8]. 2.N-terminal ubiquitination promotes degradation of N-terminally unacetylatedproteins, thus Nt-acetylation may protect proteins from this degradationpathway [15]. 3. The newly discovered N-end rulebranch involves the degradation of Ac-N-degrons via the Doa10 E3 ubiquitinligase [18]. 4. Nt-acetylation is essential for thefunctioning of actin filaments by modulating protein–proteininteractions [21]–[23]. 5. Tfs1requires its acetylated N-terminus to directly inhibit the cytosoliccarboxypeptidase CPY [24]. 6. Nt-acetylation targets theGTPases Arl3p and Grh1p to the Golgi membrane [25]–[27].7. Trm1p-II requires Nt-acetylation for proper associationto the inner nuclear membrane [28]. 8.Nt-acetylated Sir3p specifically interacts with unmethylated lysine 79 ofhistone H3 in silenced chromatin and is essential for proper gene silencing[32]. 9. Nt-acetylation preventspost-translational translocation through the ER membrane [33].
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3104970&req=5

pbio-1001074-g002: Functional effects of N-terminal acetylation. 1.Nat complexes associate with ribosomes to perform co-translationalNt-acetylation of a majority of eukaryotic proteins [8]. 2.N-terminal ubiquitination promotes degradation of N-terminally unacetylatedproteins, thus Nt-acetylation may protect proteins from this degradationpathway [15]. 3. The newly discovered N-end rulebranch involves the degradation of Ac-N-degrons via the Doa10 E3 ubiquitinligase [18]. 4. Nt-acetylation is essential for thefunctioning of actin filaments by modulating protein–proteininteractions [21]–[23]. 5. Tfs1requires its acetylated N-terminus to directly inhibit the cytosoliccarboxypeptidase CPY [24]. 6. Nt-acetylation targets theGTPases Arl3p and Grh1p to the Golgi membrane [25]–[27].7. Trm1p-II requires Nt-acetylation for proper associationto the inner nuclear membrane [28]. 8.Nt-acetylated Sir3p specifically interacts with unmethylated lysine 79 ofhistone H3 in silenced chromatin and is essential for proper gene silencing[32]. 9. Nt-acetylation preventspost-translational translocation through the ER membrane [33].
Mentions: Unlike most other protein modifications, Nt-acetylation is irreversible; it occursmainly during the synthesis of the protein, catalyzed by N-terminalacetyltransferases (NATs) associated with ribosomes [4]–[7] (Figure 1 and Figure 2, point 1). There are severaldistinct NATs in eukaryotes—NatA‐NatF—each composed of one ormore subunits and each acetylating a specific subgroup of N‐termini dependingon the amino acid sequence of the first few amino acids [8]. The Nt‐acetylationpatterns and the NAT machinery appear to be similar in all organisms from lowereukaryotes like the yeast Saccharomyces cerevisiae to highereukaryotes [1],[9], [10], althoughhigher eukaryotes have more protein Nt‐acetylation and express more NATs thanyeast do [1],[8].

Bottom Line: Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic.However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins.These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Bergen, Bergen, Norway. thomas.arnesen@mbi.uib.no

ABSTRACT
Protein N-terminal acetylation is a major modification of eukaryotic proteins. Its functional implications include regulation of protein-protein interactions and targeting to membranes, as demonstrated by studies of a handful of proteins. Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic. However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins. These contributions represent new and intriguing hypotheses that will guide the research in the years to come.

Show MeSH