Mitosis and protein Na-terminal acetylation

Dissertation presented to obtain the Ph.D degree in Developmental Biology

Protein N-terminal acetylation is a highly conserved and widespread modification that occurs on approximately 80% of all soluble, cytoplasmic human proteins. Nevertheless, with few exceptions, little is known about the biological function of protein N- acetylation. Recently, it was suggested to act as a general protein destabilization signal in yeast (Hwang et al., 2010). Yet, other reports suggest it might act as stabilizer, for instance by blocking protein degradation (Ciechanover and Ben-Saadon, 2004). This protein modification is catalyzed by N-terminal acetyltransferases (NATs), which are highly conserved from yeast to humans both in subunit composition and substrate specificity (Starheim et al., 2009). Since NATs enzymatic activity and function has been mostly studied in yeast and tissue culture cells, our current understanding of the role of these enzymes during development of multicellular organisms is extremely poor, being our main goal to understand the role of this ubiquitous protein modification during development.(...)

This dissertation was sponsored by Fundação para a Ciência e Tecnologia. Apoio financeiro da FCT e do FSE no âmbito do Quadro Comunitário de apoio, BD nº SFRH/BD/28767/2006 e projecto FCT-POCIDG/ BIA/82013/06