NterAct SIGNED
Discovery and functional significance of post-translational N-terminal acetylation
Total Cost €
0EC-Contrib. €
0Partnership
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Project "NterAct" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITETET I BERGEN
Organization address contact info |
| Coordinator Country | Norway [NO] |
| Project website | https://www.uib.no/en/rg/nat |
| Total cost | 1˙999˙273 € |
| EC max contribution | 1˙999˙273 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2017-COG |
| Funding Scheme | ERC-COG |
| Starting year | 2018 |
| Duration (year-month-day) | from 2018-06-01 to 2023-05-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITETET I BERGEN | NO (BERGEN) | coordinator | 1˙999˙273.00 |
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Project objective
In mammalian cells, N-terminal (Nt) acetylation is one of the most abundant protein modifications. It is catalysed by N-terminal acetyltransferases (NATs) and mostly occurs co-translationally. However, in contrast to the defined co-translational NATs, post-translational NATs which have crucial regulatory roles are mostly unexplored. Distinct peptide hormones regulate appetite, metabolism, sexual behaviour and pain, and their biological activity is critically modulated by post-translational Nt-acetylation. However, the identity of the NAT responsible for this modification, ‘HormNat’, is unknown, thus the molecular and physiological ramifications of this regulatory circuit remain elusive. Another example is actin, a key regulator of cell motility and cell division. The actin N-terminus is crucial for actin function and in mammals actin is modified by an unknown post-translational NAT, ‘ActNat’. Hence, the objectives of this project are to identify these human NATs acting post-translationally, and to investigate their molecular mechanisms, regulation and impact.
We will identify the novel NATs by a combination of classical and newly developed in-house tools like in vitro acetylation assays, unique bisubstrate analogues, Nt-acetylation specific antibodies, and targeted mass spectrometry. Interestingly, Nt-acetylation is considered irreversible, but there is reason to believe that specific substrates are Nt-deacetylated. Elucidation of post-translational NATs and the reversible nature of Nt-acetylation would represent a new era in the field of protein and peptide regulation and identify key cellular and organismal switches.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Henriette Aksnes, Rasmus Ree, Thomas Arnesen Co-translational, Post-translational, and Non-catalytic Roles of N-Terminal Acetyltransferases published pages: 1097-1114, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.02.007 |
Molecular Cell 73/6 | 2020-01-30 |
| 2018 |
Henriette Aksnes, Michael Marie, Thomas Arnesen, Adrian Drazic Actin polymerization and cell motility are affected by NAA80-mediated posttranslational N-terminal acetylation of actin published pages: e1526572, ISSN: 1942-0889, DOI: 10.1080/19420889.2018.1526572 |
Communicative & Integrative Biology 11/4 | 2020-01-30 |
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