000406950 001__ 406950
000406950 005__ 20230212180951.0
000406950 0247_ $$2CORDIS$$aG:(EU-Grant)772039$$d772039
000406950 0247_ $$2CORDIS$$aG:(EU-Call)ERC-2017-COG$$dERC-2017-COG
000406950 0247_ $$2originalID$$acorda__h2020::772039
000406950 035__ $$aG:(EU-Grant)772039
000406950 150__ $$aDiscovery and functional significance of post-translational N-terminal acetylation$$y2018-06-01 - 2023-05-31
000406950 371__ $$aUniversity of Bergen$$bUniversity of Bergen$$dNorway$$ehttp://www.uib.no/en/node/36362$$vCORDIS
000406950 372__ $$aERC-2017-COG$$s2018-06-01$$t2023-05-31
000406950 450__ $$aNterAct$$wd$$y2018-06-01 - 2023-05-31
000406950 5101_ $$0I:(DE-588b)5098525-5$$2CORDIS$$aEuropean Union
000406950 680__ $$aIn 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.
000406950 909CO $$ooai:juser.fz-juelich.de:849425$$pauthority$$pauthority:GRANT
000406950 909CO $$ooai:juser.fz-juelich.de:849425
000406950 970__ $$aoai:dnet:corda__h2020::41ee4ea85aa7e6d3b9b0f55fc7a27004
000406950 980__ $$aG
000406950 980__ $$aCORDIS
000406950 980__ $$aAUTHORITY