Modifying Deubiquitinases: Protein ubiquitination is a widespread mechanism for cellular regulation, and new regulators are valuable research tools and may help to generate therapeutic small molecules. Ernst et al. (p. 590 , published online 3 January) used known crystal structures to roughly define the interaction domain between a ubiquitin-specific protease and a ubiquitinated substrate and then screened ubiquitin variants with changes in these residues to find variants that acted as potent and specific regulators that could modify ubiquitin pathway regulation in cells.

NODs require S-palmitoylation to signal: The compartmentalization of proteins within the cell is essential for their function. The addition of lipid molecules redistributes proteins to the cell surface or to membrane-bound organelles. Working in transgenic mice and in tissue cultured cells, Lu et al. found that nucleotide oligomerization domain–like receptors 1 and 2 (NOD1 and NOD2), two proteins responsible for detecting bacterial products, required lipid modifications for their recruitment to the cell membrane and function. The specific modification, palmitoylation at a cysteine thiol, was mediated by the enzyme ZDHHC5. Loss of ZDHHC5 or removal of key modification residues in NOD1 and NOD2 abolished their function, compromising antibacterial responses. Human variants of NOD2 display altered palmitoylation, which could help to explain many inflammatory conditions, such as irritable bowel syndrome. Science , this issue p. 460