Acetylation articles from across Nature Portfolio

Most individuals with primary familial brain calcification (PFBC) remain genetically unsolved. Here the authors show that NAA60 biallelic variants cause PFBC, likely via reduced N-terminal acetylation and SLC20A2 levels with impaired phosphate uptake.

Microtubules are acetylated on the inside of their hollow lumen, a modification linked to their lifespan. Here, the authors show that damage holes act as entry points for a deacetylase to access the lumen, thereby locally counteracting acetylation.

Human protein DJ-1 displays neuroprotective properties. Here, the authors demonstrate that DJ-1 hydrolyzes cyclic 3-phosphoglyceric anhydride (cPGA), thereby protecting proteins from acylation by this highly reactive metabolite spontaneously forming in glycolysis.

Here the authors report a strategy to directly capture substrates of lysine-modifying enzymes via post-translational modification (PTM)-acceptor residue crosslinking in living cells, enabling global profiling of substrates of PTM-enzymes and validation of PTM-sites in a straightforward manner.

Protein S-acylation is involved in many pathophysiological processes. Here, Mesquita et al. discuss the structure, function and regulation of S-acylation and deacylation enzymes and describe how this post-transcriptional modification precisely controls protein–cell membrane interactions. Potential therapeutic applications of S-acylation are also highlighted.

Thomas Arnesen and colleagues discuss an emerging major role of one of the most common protein modifications, N-terminal acetylation, in shielding the proteome from degradation.

Mitochondrial proteins are frequently acetylated, but most of these modifications are thought to occur non-enzymatically, rather than requiring an acetyltransferase. A new study by Akhtar and colleagues challenges this view by demonstrating that MOF, a well-characterized histone acetyltransferase, bolsters mitochondrial metabolism by acetylating the complex IV assembly factor COX17.

Transactivation hubs and related biomolecular condensates are emerging as relevant molecular players in cancer biology. A new study now links PD-L1 upregulation on the cancer cell surface and IRF1–KAT8 transactivation hubs at PD-L1 loci. Therapeutic targeting of these hubs holds potential to unleash antitumor immunity.

Sirtuins are highly conserved enzymes with key roles in life extension in multiple organisms. A study now describes selective autophagic degradation of nuclear SIRT1 in senescent cells. These observations suggest that blocking sirtuin degradation could be a potential approach for anti-ageing therapies.

PD-L1 has been extensively described as the membrane-bound ligand of PD-1. A recent study discovered a previously unknown role for PD-L1, which is able to bind DNA and thus govern different pathways linked to either evasion of immune surveillance or tumour microenvironment inflammation.