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- _4 wasQuotedFrom 15138278 provenance.
- _4 value "Orlistat reduced phosphorylation of the Rb protein, up-regulated p27Kip1, and down-regulated Skp2. These effects were evident at levels of the drug consistent with the cellular IC50 of Orlistat for inhibition of the FAS thioesterase (1-3 M). To independently verify that the effects of Orlistat could be attributed to its ability to block FAS, similar experiments were conducted with siRNA-targeting FAS (Fig. 4B). Like Orlistat, the siRNA-targeting FAS decreased the phosphorylation of Rb, increased the level of p27Kip1, and reduced the level of Skp2. An siRNA-targeting Skp2 had identical effects upon its downstream target, p27Kip1, and upon the phosphorylation status of the Rb protein. Together, these findings provide strong support for the idea that a FAS blockade acts upon the Rb pathway via regulation of Skp2 and also indicate that a FAS blockade is likely to have effects similar to an Skp2 blockade." provenance.