Finding Folliculin's Function

Abstract

Cell Signaling The tumor-suppressor protein folliculin (FLCN) is turning up as an important component of distinct cell signaling pathways that control cell growth and metabolism. FLCN's structure provides no recognizable clues to its function, but mutations in FLCN cause a cancer syndrome in humans. Exactly how it does so has remained unclear. Recent work showed that FLCN can act as a GAP (guanosine triphosphatase—activating protein) to control the kinase mTORC1, which regulates cell growth. Possik et al. report that FLCN binds to and inhibits another key regulatory kinase, AMPK (adenosine monophosphate–activated protein kinase), which helps maintain energy balance in the cell. Loss of FLCN acts through AMPK to help cells resist stresses such as starvation. This effect was mediated, at least in part, by increased autophagy. These results suggest that the loss of FLCN function in cancer cells may make them more tolerant of stress and thus more effective at invading tissues of the host organism. PLOS Genet. 10.1371/journal.pgen.1004273 (2014).