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Catalyzed by different N\u2010terminal acetyltransferases (NATs), N\u2010Ac was originally believed to mostly promote protein stability. However, several functional consequences at substrate level were recently described that yielded important new insights about the distinct molecular functions for this modification. The ubiquitous and apparent irreversible nature of this protein modification leads to the assumption that N\u2010Ac mostly executes constitutive functions. In spite of the large number of substrates for each NAT, recent studies in multicellular organisms have nevertheless indicated very specific phenotypes after NAT loss. This raises the hypothesis that in vivo N\u2010Ac is only functionally rate limiting for a small subset of substrates. In this review, we will discuss the function of N\u2010Ac in the context of a developing organism. We will propose that some rate limiting NAT substrates may be tissue\u2010specific leading to differential functions of N\u2010Ac during development of multicellular organisms. Moreover, we will also propose the existence of tissue and developmental\u2010specific mechanisms that differentially regulate N\u2010Ac.<\/jats:p>","DOI":"10.1002\/pmic.201400631","type":"journal-article","created":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T06:33:54Z","timestamp":1430289234000},"page":"2402-2409","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Developmental roles of protein N\u2010terminal acetylation"],"prefix":"10.1002","volume":"15","author":[{"given":"Rui D.","family":"Silva","sequence":"first","affiliation":[{"name":"Departamento de Ci\u00eancias Biom\u00e9dicas e Medicina and Center for Biomedical Research Universidade do Algarve, Campus de Gambelas  Faro Portugal"}]},{"given":"Rui G.","family":"Martinho","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Biom\u00e9dicas e Medicina and Center for Biomedical Research Universidade do Algarve, Campus de Gambelas  Faro Portugal"},{"name":"Instituto Gulbenkian de Ci\u00eancia  Oeiras Portugal"}]}],"member":"311","published-online":{"date-parts":[[2015,6,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/S0021-9258(17)33793-6","article-title":"Evidence that approximately eighty per evidence that approximately eighty per cent of the soluble proteins from ehrlich ascites cells are nalpha\u2010acetylated","volume":"251","author":"Brown J. 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