|Protein N-terminal acetylation - From molecular mechanisms to human disease||Prof. Thomas Arnesen | University of Bergen, Norway|
Protein N-terminal acetylation is among the most common types of protein modifications occurring on approximately 50 % of all soluble yeast proteins and more than 80 % of all soluble human proteins. Surprisingly, there is yet no clear functional understanding of how N-terminal acetylation affects proteins in general, although recent data indicate roles in protein degradation and targeting. During the last six years, the human NATs have been identified and characterized by our group. In humans as in yeast, three NAT complexes NatA, NatB and NatC are believed to perform most N-terminal acetylations. The importance of N-terminal acetylation in human cell biology and disease has been increasingly recognized.
The human NatA complex is the major N-terminal acetyltransferase in humans cotranslationally acetylating nascent polypeptides with Ala-, Ser-, Thr-, Val- or Gly- N-termini after cleavage of the initiator Met. An increasing interest to the hNatA complex results from recent findings demonstrating correlation between expression of the hNatA subunits and tumour development. Functional studies of hNatA revealed that its subunits are essential for the maintenance of growth and survival of several cancer cell types, and knockdown of NatA sensitized cancer cells to drug treatment. Taken together, hNatA may be a potential target for cancer therapy.