Consistent with its putative tumour suppressor role, FLCN has been shown to directly regulate cell cycle progression.
FLCN has been shown to inhibit cyclin D1 expression through an unknown mechanism (Kawai et al., 2013). Cyclin D1 is required to promote G1 to S transition, suggesting that FLCN functions to halt this transition.
FLCN phosphorylation changes throughout the cell cycle, with S302 phosphorylation highest during G1 phase, and ser62 and ser73 phosphorylation highest during mitosis (Dephoure et al., 2008; Laviolette et al., 2013). Laviolette et al., (2013) showed that FLCN acts to slow down cell cycle progression and becomes phosphorylated at ser62 and ser73 as the cell cycle progresses. The authors also show that ser62 and ser73 phosphorylation reduces FLCN’s stability, suggesting that FLCN may be degraded during mitosis in order to allow cells to divide (Laviolette et al., 2013).