In Cell this week, a team led by researchers at the University of Wisconsin-Madison shows that the mitochondrial deacetylase "Sirt3 is an essential player in enhancing the mitochondrial glutathione antioxidant defense system" during caloric restriction in mice, and that consequently, it "slows the progression of age-related hearing loss." The team found that, in wild-type mice, caloric restriction "reduces oxidative DNA damage in multiple tissues and prevents AHL," but it does not do so in mice lacking Sirt3. In their in vitro investigations, the researchers found that overexpression of Sirt3 and/or isocitrate dehydrogenase 2 protects cultured cells from oxidative stress-induced death.
Over in Cell Host & Microbe this week, investigators at the Mount Sinai School of Medicine and their colleagues at Columbia and the University of California, Berkeley, show that an essential component of the type I interferon signaling pathway, mouse STAT2, "restricts early dengue virus replication in vivo." Using STAT2-knockout mice, the team found that the interferon antagonist NS5 protein binds in a species-specific manner; the "difference in NS5-mediated binding and degradation between human and mouse STAT2 maps to a region within the STAT2 coiled-coil domain," the authors write.
Investigators at the Dana-Farber Cancer Institute and the Salk Institute have determined that "a stapled p53 helix preferentially targets HDMX, blocks the formation of inhibitory p53-HDMX complexes, induces p53-dependent transcriptional upregulation, and thereby overcomes HDMX-mediated cancer resistance in vitro and in vivo." They report a detailed analysis of p53-HDMX complexes and their functions in Cancer Cell this week. The Dana-Farber-led team says that their study "provides a blueprint for reactivating the p53 pathway in cancer by matching HDM2, HDMX, or dual inhibitors to the appropriate cellular context."
In another Cancer Cell paper published this week, researchers at the University of Michigan show that many markers of phenotypic heterogeneity among tumorigenic melanoma cells seem "to be reversibly expressed." More specifically, in their mouse model investigations, the UMich researchers found that "all tumorigenic cells appeared to have unlimited tumorigenic capacity on serial transplantation," and further, that "some melanomas metastasized in mice, irrespective of whether they arose from CD271− or CD271+ cells."