Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase

The target of rapamycin (TOR) plays a central role in eukaryotic cell growth control. With prevalent hyperactivation of the mammalian TOR (mTOR) pathway in human cancers, strategies to enhance TOR pathway inhibition are needed. We used a yeast-based screen to identify small-molecule enhancers of rapamycin (SMERs) and discovered an inhibitor (SMER3) of the Skp1-Cullin-F-box (SCF)^(Met30) ubiquitin ligase, a member of the SCF E3-ligase family, which regulates diverse cellular processes including transcription, cell-cycle control and immune response. We show here that SMER3 inhibits SCF^(Met30) in vivo and in vitro, but not the closely related SCF^(Cdc4). Furthermore, we demonstrate that SMER3 diminishes binding of the F-box subunit Met30 to the SCF core complex in vivo and show evidence for SMER3 directly binding to Met30. Our results show that there is no fundamental barrier to obtaining specific inhibitors to modulate function of individual SCF complexes

Invertebrate Scavenging Communities

Invertebrate scavengers of terrestrial and aquatic carrion include a broad and enormously diverse grouping of various arthropods, nematodes, and molluscs. By far the most functionally important in terrestrial ecosystems are insects, especially the flies, with crustaceans performing this role in marine ecosystems, although a multi-trophic foodweb of numerous invertebrate taxa can be found at most carcasses in most environments. The occurrence of different taxa, and the dynamics of their colonization and various competitive interactions varies across terrestrial and aquatic realms, and is greatly influenced by geographic region, climate, habitat, season, and other biotic factors. This sub-chapter focuses on the invertebrate use of carrion in both terrestrial and aquatic ecosystems, and highlights the role of different groups of invertebrates, and the biotic and abiotic factors that influence their occurrence and succession at decaying carcasses