Raising the list of SirT7 targets to a new level

Sirtuins are crucial proteins involved in sensing and coordinating the response to different forms of stress, mainly through NAD(+)-dependent deacetylation of proteins. For that reason, sirtuins are directly involved in many human pathologies including cancer, diabetes, cardiovascular and neurodegenerative diseases. SirT7, one of the less well-understood sirtuins, has been associated with ribosome biogenesis, gene expression, metabolism and cancer. Despite the wide range of these functions, only a handful of targets for SirT7 have so far been described. In this issue, Zhang et al. report the first proteomic screening of SirT7 substrates. Using stable isotope labeling with amino acids in cell culture (SILAC), coupled with quantitative mass spectrometry, they have identified a comprehensive list of candidates involved in a variety of functions, ranging from maintenance of chromatin architecture to gene silencing and metabolism. A selected group of these candidates has been validated by in vitro co-immunoprecipitation and deacetylation experiments. Predictive tools have identified additional candidates. The identification of these novel targets not only suggests new ways of understanding the physiological role of SirT7, but also provides new evidence to add to our existing knowledge of the global impact of sirtuins in cell homeostasis.