NAA60 (HAT4): the newly discovered bi-functional Golgi member of the acetyltransferase family

Abstract

Chromatin structural organization, gene expression and proteostasis are intricately regulated in a wide range of biological processes, both physiological and pathological. Protein acetylation, a major post-translational modification, is tightly involved in interconnected biological networks, modulating the activation of gene transcription and protein action in cells. A very large number of studies describe the pivotal role of the so-called acetylome (accounting for more than 80% of the human proteome) in orchestrating different pathways in response to stimuli and triggering severe diseases, including cancer. NAA60/NatF (N-terminal acetyltransferase F), also named HAT4 (histone acetyltransferase type B protein 4), is a newly discovered acetyltransferase in humans modifying N-termini of transmembrane proteins starting with M–K/M-A/M-V/M-M residues and is also thought to modify lysine residues of histone H4. Because of its enzymatic features and unusual cell localization on the Golgi membrane, NAA60 is an intriguing acetyltransferase that warrants biochemical and clinical investigation. Although it is still poorly studied, this review summarizes current findings concerning the structural hallmarks and biological role of this novel targetable epigenetic enzyme.

Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections

“…Different studies indicate that NatF is found only in higher eukaryotes, localizes to the Golgi membranes, acetylates transmembrane proteins, and is probably involved in Golgi structural organization [188,189]. Additionally, the dual behavior of NatF as a histone acetyltransferase (Hat) and as Nat has been reported [190], indicating that NatF plays a role in epigenetics. The presence of NatF in T. cruzi has also been suggested [35].…”