The nuclear factor κB (NF-κB) family of inducible transcription factors regulates the expression of a large number of target genes involved in immune and inflammatory responses, apoptosis and cell proliferation, differentiation and survival. Previous studies have shown that acetylation of p65, one of the five mammalian NF-κB family members, has an important role in the regulation of NF-κB-dependent transcription. Now, Michael Hottiger and colleagues (p. 4251) characterise SIRT2, a member of the sirtuin family of NAD⁺-dependent histone deacetylases, as a p65 deacetylase. The authors show that SIRT2 interacts with p65 in the cytoplasm of mouse embryonic fibroblasts, and deacetylates p65 in vitro and in vivo at Lys310. They report that p65 is hyperacetylated at this residue in Sirt2^−/− cells after stimulation with TNFα, a proinflammatory cytokine that induces NF-κB activation and nuclear translocation. Importantly, hyperacetylation of p65 in Sirt2^−/− cells results in an increase in the expression of a subset of p65 acetylation-dependent target genes. On the basis of these and other results, the authors propose that deacetylation of p65 by SIRT2 in the cytoplasm is an important regulator of TNFα-induced NF-κB-dependent gene expression.

• © 2010.