Reviews & Perspectives
- Every year, a major cause of human disease and death worldwide is infection with the various pathogens—viruses, bacteria, fungi, and protozoa—that are intrinsic to our ecosystem. In efforts to control the prevalence of infectious disease and develop improved therapies, the scientific community has focused on building a molecular picture of pathogen infection and spread. These studies have been aimed at defining the cellular mechanisms that allow pathogen entry into hosts cells, their replication and transmission, as well as the core mechanisms of host defense against pathogens.
- Sirtuin 6 (SIRT6), a member of the mammalian sirtuin family, is a nuclear deacetylase with substrate-specific NAD+-dependent activity. SIRT6 has emerged as a critical regulator of diverse processes, including DNA repair, gene expression, telomere maintenance, and metabolism. However, our knowledge regarding its interactions and regulation remains limited. Here, we present a comprehensive proteomics-based analysis of SIRT6 protein interactions and their dependence on SIRT6 catalytic activity. We also identify evolutionarily conserved SIRT6 phosphorylations, including four within a proline-rich disordered region, and show that the conserved S338 phosphorylation can modulate selected SIRT6 interactions.
- Much like the host cells they infect, viruses must also regulate their life cycles. Herpes simples virus type 1 (HSV-1), a prominent human pathogen, uses a promoter-rich genome in conjunction with multiple viral trans-activating factors. Following entry into host cells, the virion-associated outer tegument proteins pUL46 and pUL47 act to increase expression of viral immediate–early (α) genes, thereby helping initiate the infection life cycle. Because pUL46 has gone largely unstudied, we employed a hybrid mass spectrometry-based approach to determine how pUL46 exerts its functions during early stages of infection.