Protein N-terminal acetyltransferases: when the start matters

Trends Biochem Sci. 2012 Apr;37(4):152-61. doi: 10.1016/j.tibs.2012.02.003. Epub 2012 Mar 7.


The majority of eukaryotic proteins are subjected to N-terminal acetylation (Nt-acetylation), catalysed by N-terminal acetyltransferases (NATs). Recently, the structure of an NAT-peptide complex was determined, and detailed proteome-wide Nt-acetylation patterns were revealed. Furthermore, Nt-acetylation just emerged as a multifunctional regulator, acting as a protein degradation signal, an inhibitor of endoplasmic reticulum (ER) translocation, and a mediator of protein complex formation. Nt-acetylation is regulated by acetyl-coenzyme A (Ac-CoA) levels, and thereby links metabolic cell states to cell death. The essentiality of NATs in humans is stressed by the recent discovery of a human hereditary lethal disease caused by a mutation in an NAT gene. Here, we discuss how these recent findings shed light on NATs as major protein regulators and key cellular players.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Animals
  • Humans
  • Models, Biological
  • Proteins / metabolism


  • Proteins
  • Acetyltransferases
  • protein N-terminal acetyltransferase